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| 1 | Bone Morphogenetic Protein (BMP) signaling in development and human diseases显示文摘Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling. | Richard N.Wang Jordan Green Zhongliang Wang Youlin Deng Min Qiao Michael Peabody Qian Zhang Jixing Ye Zhengjian Yan Sahitya Denduluri Olumuyiwa Idowu Melissa Li Christine Shen Alan Hu Rex C.Haydon Richard Kang James Mok Michael J.Lee Hue L.Luu Lewis L.Shi | 2014 | Genes & Diseases2014，1，1： | 47 |
| 2 | Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis显示文摘As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. | Yixiao Feng Mia Spezia Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren | 2018 | Genes & Diseases2018，5，2： | 24 |
| 3 | The versatile functions of Sox9 in development,stem cells,and human diseases显示文摘The transcription factor Sox9 was first discovered in patients with campomelic dysplasia,a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis.Since then,its role as a cell fate determiner during embryonic development has been well characterized;Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and organs.However,recent data has shown that ectoderm-and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools,suggesting its role in cell maintenance and specification during adult life.The versatility of Sox9 may be explained by a combination of posttranscriptional modifications,binding partners,and the tissue type in which it is expressed.Considering its importance during both development and adult life,it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases,including fibrosis and cancer.This review provides a summary of the various roles of Sox9 in cell fate specification,stem cell biology,and related human diseases.Ultimately,understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage. | Alice Jo Sahitya Denduluri Bosi Zhang Zhongliang Wang Liangjun Yin Zhengjian Yan Richard Kang Lewis L.Shi James Mok Michael J.Lee Rex C.Haydon | 2014 | Genes & Diseases2014，1，2： | 16 |
| 4 | Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism显示文摘Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood. | Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou | 2020 | Genes & Diseases2020，7，2： | 9 |
| 5 | Multifaceted signaling regulators of chondrogenesis:Implications in cartilage regeneration and tissue engineering显示文摘Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature.Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue.Here,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue engineering.These include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling pathways.Transcriptional and epigenetic regulation of chondrogenesis will also be discussed.Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering. | Jordan D.Green Viktor Tollemar Mark Dougherty Zhengjian Yan Liangjun Yin Jixing Ye Zachary Collier Maryam K.Mohammed Rex C.Haydon Hue H.Luu Richard Kang Michael J.Lee Sherwin H.Ho Tong-Chuan He Lewis L.Shi Aravind Athiviraham | 2015 | Genes & Diseases2015，2，4： | 9 |
| 6 | Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference显示文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics. | Shujuan Yan Ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C.Haydon Michael J.Lee Russell R.Reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng | 2018 | Genes & Diseases2018，5，2： | 8 |
| 7 | Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside显示文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care. | Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He Russell R.Reid | 2019 | Genes & Diseases2019，6，4： | 6 |
| 8 | Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer显示文摘The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy resistance.Therefore,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment.Ferroptosis is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer development.Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis.This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment. | Feifei Pu Fengxia Chen Zhicai Zhang Deyao Shi Binlong Zhong Xiao Lv Andrew Blake Tucker Jiaming Fan Alexander J.Li Kevin Qin Daniel Hu Connie Chen Hao Wang Fang He Na Ni Linjuan Huang Qing Liu William Wagstaff Hue H.Luu Rex C.Haydon Le Shen Tong-Chuan He Jianxiang Liu Zengwu Shao | 2022 | Genes & Diseases2022，9，2： | 6 |
| 9 | Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)显示文摘Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions. | Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi Zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan Linghuan Zhang Yixiao Feng Wei Liu Bo Huang Bo Zhang Wenping Luo Xi Wang Bo Liu Rex C.Haydon Hue H.Luu Tong-Chuan He Hua Gan | 2018 | Genes & Diseases2018，5，2： | 5 |
| 10 | Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system显示文摘Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vectors.However,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression.The piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian cells.Despite its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation flexibilities.Here,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac system.By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase plasmid.We further determine the drug selection timeline to achieve optimal stable transgene expression.Moreover,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors.Using the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high efficiency.Thus,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression. | Xiang Chen Jing Cui Zhengjian Yan Hongmei Zhang Xian Chen Ning Wang Palak Shah Fang Deng Chen Zhao Nisha Geng Melissa Li Sahitya K.Denduluri Rex C.Haydon Hue H.Luu Russell R.Reid Tong-Chuan He | 2015 | Genes & Diseases2015，2，1： | 5 |
| 11 | Transition to resistance:An unexpected role of the EMT in cancer chemoresistance显示文摘Two recent studies provide intriguing evidence that challenges the role of the epithelialemesenchymal transition(EMT)as a critical mediator of cancer metastasis,while revealing an unexpected role in cancer drug resistance.1,2 While these findings may not settle the EMT’s role in metastasis,these studies suggest that targeting the EMT may inhibit both cancer metastasis and chemoresistance. | Jing Wang Qiang Wei Xin Wang Shengli Tang Hao Liu Fugui Zhang Maryam K.Mohammed Jiayi Huang Dan Guo Minpeng Lu Feng Liu Jianxiang Liu Chao Ma Xue Hu Rex C.Haydon Tong-Chuan He Hue H.Luu | 2016 | Genes & Diseases2016，3，1： | 4 |
| 12 | The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs显示文摘While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders. | Zongyue Zeng Bo Huang Shifeng Huang Ruyi Zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen Zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Rex C.Haydon Hue H.Luu Lan Zhou Russell R.Reid Tong-Chuan He Xingye Wu | 2018 | Genes & Diseases2018，5，1： | 4 |
| 13 | An NgAgo tool for genome editing:did CRISPR/Cas9 just find a competitor?显示文摘While CRISPR/Cas9-mediated genome editing technology has been experiencing a rapid transformation during the past few years,a recent report on NgAgo-mediated singlestranded DNA-guided genome editing may offer an attractive alternative for genome manipulation.While it’s too early to predict whether NgAgo will be able to compete with or be superior to CRISPR/Cas9,the scientific community is anxiously waiting for further optimization and broader applications of the NgAgo genome editing technology. | Qiang Wei Junyi Liao Xinyi Yu Eric J.Wang Claire Wang Hue H.Luu Rex C.Haydon Michael J.Lee Tong-Chuan He | 2016 | Genes & Diseases2016，3，3： | 2 |
| 14 | Melanoma:Molecular genetics,metastasis,targeted therapies,immunotherapies,and therapeutic resistance显示文摘Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s.For some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options.Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF,NRAS,and TERT genes,some of which can be therapeutically targeted.Though initially effective,many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways.Immunotherapies represent an alternative to molecular targeted therapies.However,inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term.As the protocol for combination therapies develop,so will our scientific understanding of the many pathways at play in the progression of melanoma.The future direction of the field may be to find a molecule that connects all of the pathways.Meanwhile,noncoding RNAs have been shown to play important roles in melanoma development and progression.Studying noncoding RNAs may help us to understand how resistance e both primary and acquired e develops;ultimately allow us to harness the true potential of current therapies.This review will cover the basic structure of the skin,the mutations and pathways responsible for transforming melanocytes into melanomas,the process by which melanomas metastasize,targeted therapeutics,and the potential that noncoding RNAs have as a prognostic and treatment tool. | William Wagstaff Rimel N.Mwamba Karina Grullon Mikhayla Armstrong Piao Zhao Bryce Hendren-Santiago Kevin H.Qin Alexander J.Li Daniel A.Hu Andrew Youssef Russell R.Reid Hue H.Luu Le Shen Tong-Chuan He Rex C.Haydon | 2022 | Genes & Diseases2022，9，6： | 2 |
| 15 | Opening the LOX to bone metastasis: The role of secreted lysyl oxidase in skeletal recurrence of breast cancers显示文摘Breast cancer is the second-most prevalent cancer in the United States,with 234,190 new cases projected to be diagnosed in 2015.The initial diagnosis is commonly made early in its disease course due to the use of routine screening mammography.1 Combined with advances in adjuvant chemotherapy,this has led to promising overall outcomes,including a 5-year survival rate of 89.4%and a 10%e12%rate of locoregional recurrence at 20 years for stage I/II disease.1-3 By comparison,prognosis remains poor for patients with metastatic disease at diagnosis or for those who present after initial cure of disease with distant recurrence.4 Among cases of distant recurrence,skeletal recurrence occurs frequently and can be accompanied by hypercalcemia,pain,and functional compromise often requiring a protracted course of palliative therapy. | Maryam K.Mohammed Connie Shao Hue H.Luu Rex C.Haydon | 2015 | Genes & Diseases2015，2，4： | 1 |
| 16 | Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)显示文摘Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role in maintaining the homeostasis of gut epithelium.In 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in vitro.Since then,the intestinal organoid technology has been used to delineate cellular signaling in ISC biology.However,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional organoids.Thus,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic manipulations.In this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression system.We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional culture.While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo.Collectively,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis. | Xiaoxing Wu Zhaoxia Li Hongyu Zhang Fang He Min Qiao Huaxiu Luo Jing Zhang Meng Zhang Yukun Mao William Wagstaff Yongtao Zhang Changchun Niu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu Rex C.Haydon Russell R.Reid Hue H.Luu Tong-Chuan He Ziwei Wang Houjie Liang Bing-Qiang Zhang Ning Wang | 2021 | Genes & Diseases2021，8，6： | 1 |
| 17 | Argonaute(AGO)proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells(MSCs)显示文摘As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs.However,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood.Emerging evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone formation.As highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA biogenesis.Here,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs.We first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in MSCs.By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in MSCs.Furthermore,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone formation.Collectively,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs. | Yukun Mao Na Ni Linjuan Huang Jiaming Fan Hao Wang Fang He Qing Liu Deyao Shi Kai Fu Mikhail Pakvasa William Wagstaff Andrew Blake Tucker Connie Chen Russell R.Reid Rex C.Haydon Sherwin H.Ho Michael J.Lee Tong-Chuan He Jian Yang Le Shen Lin Cai Hue H.Luu | 2021 | Genes & Diseases2021，8，6： | 1 |
| 18 | Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis显示文摘As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. | Yixiao Feng Mia Spezia Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren | 2018 | Genes & Diseases2018，5，3： | 0 |
| 19 | Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering显示文摘Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration. | Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He Jiaming Fan | 2022 | Bioactive Materials2022，7，3： | 0 |
| 20 | SV40 large T antigen-induced immortalization reprograms mouse cardiomyocyte progenitors with mesenchymal stem cell characteristics and osteogenic potential显示文摘While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(CPs)have a limited life span in culture,hampering the use of CPs for in vitro and in vivo studies.We previously isolated primary CPs from mouse E15.5 fetal heart,and reversibly immortalized them with SV40 large T antigen(SV40 LTA),resulting in immortalized CPs(iCPs),which maintain long-term proliferation and ex-press cardiomyogenic markers and retain differentiation potential under appropriate differentiation conditions. | Yichun Yu Jiamin Zhong Connie Chen Yannian Gou Guozhi Zhao Piao Zhao Yonghui Wang Wei Zeng Annie Wang William D.Wagstaff Jr Rex C.Haydon Tong-Chuan He Russell R.Reid Michael J.Lee Hue H.Luu Jiaming Fan | 2023 | Genes & Diseases2023，10，4： | 0 |
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