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| 1 | Single-cell transcriptomes and runx2b^(-/-)mutants reveal the genetic signatures of intermuscular bone formation in zebrafish显示文摘Intermuscular bones(IBs)are mineralized spicules,present in the myosepta of many,but not all,teleost species.IBs are often small and sharp,and they consequently limit how the fish can be processed;the IBs may cause injury or trauma if lodged in consumers’throats or mouths,and therefore affect the appeal of the fish to many consumers.The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established.Here,the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish.The analysis defined 18 distinct cell types.Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation.In particular,the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants.Among those,runx2b^(-/-)mutants completely lost IBs,while swimming performance,growth and bone mineral density were not significantly different from runx2b^(+/+)zebrafish.Comparative single-cell RNA sequencing(sc RNA-seq)analysis in runx2b^(-/-)and runx2b^(+/+)zebrafish revealed the role of osteoblasts in IB formation.In addition,differentially expressed genes were enriched in the transforming growth factorβ/bone morphogenetic protein(TGF-β/BMP)pathway after runx2b deletion.This study provides evidence for the crucial role of runx2b regulation in IB formation.Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs,which can improve the safe consumption and economic value of many farmed fish species. | Chun-Hong Nie Shi-Ming Wan Yu-Long Chen Ann Huysseune Ya-Ming Wu Jia-Jia Zhou Alexandre Wagner Silva Hilsdorf Wei-Min Wang Paul Eckhard Witten Qiang Lin Ze-Xia Gao | 2022 | National Science Review2022，9，11： | 6 |
| 2 | 3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease显示文摘Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and IVDD.Deep learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD. | Erika Kague Francesco Turci Elis Newman Yushi Yang Kate Robson Brown Mona S.Aglan Ghada A.Otaify Sarnia A.Temtamy Victor L.Ruiz-Perez Stephen Cross C.Patrick Royall P.Eckhard Witten Chrissy L.Hammond | 2021 | Bone Research2021，9，4： | 2 |
| 3 | The WEKA data mining software显示文摘 | Mark Hall Eibe Frank Geoffrey Holmes Bernhard Pfahringer Peter Reutemann Ian H. Witten | 2009 | ACM SIGKDD Explorations Newsletter2009，，1： | 2 |
| 4 | Supersymmetry and morse theory显示文摘 | Witten E | 1982 | J Diff Geom1982，17，： | 1 |
| 5 | Arithmetic Coding for Data Compression 显示文摘 | Neal Radford M Cleary John G | 1987 | Communications of the ACM1987，30，6： | 1 |
| 6 | Arithmetic coding for data compression显示文摘 | WITTEN I NEAL R CLEARY J | 1987 | Communications of the ACM1987，30，6： | 1 |
| 7 | Arithmetic coding for data compression 显示文摘 | Witten Ian H Neal Radford M Cleary John G | 1987 | Communications of the Association for Computing Machinery1987，30，6： | 1 |
| 8 | Capillary flow as the cause of ring stains from dried liquid drops显示文摘 | Deegan R D Bakajin O Dupont T F Huber G Nagel S R Witten T A | | 0，，6653： | 1 |
| 9 | Cosmic Separation of Phases显示文摘 | Witten E | 1984 | Phys Rev D1984，30，2： | 1 |
| 10 | On-line and off-line heuristics for inferring hierarchies of repetitions in sequence显示文摘 | Neill-Manning C Witten I | 2000 | Proceedings of the IEEE2000，88，11： | 1 |
| 11 | Diffusion - limited aggregation:A kinetic critical phenomenon显示文摘 | Witten T A Sander L M | 1981 | Phys Rev Lett1981，47，19： | 1 |
| 12 | Effective harmonic-fluid approach to low-energy properties of one-dimensional quantum fluids 显示文摘 | Witten T A Sander L M | 1981 | PhysRevLet1981，47，25： | 1 |
| 13 | Long-range correlations in smoke-particle aggregates 显示文摘 | S R Forrest T A Witten Jr | 1979 | J Phys A1979，12，： | 1 |
| 14 | Tune retrieval in multimedia library显示文摘 | McNab R J Smith L A Witten I H | 2000 | Multimedia Tools And Applications2000，10，4： | 1 |
| 15 | Diffusion-Limited Aggregation,a Kinetic Critical Phenomenon显示文摘 | Witten T A Sander L M | 1981 | Physical Review Letters1981，，47： | 1 |
| 16 | Extending Greenstone for Institutional Repositories 显示文摘 | Bainbridge D Osborn W Witten I Nichols D | 2006 | ICADL2006，，： | 1 |
| 17 | Incidence and risk factors of the post- thrombotic syndrome 显示文摘 | DE WOLF MA WITTENS CH KAHN SR | 2012 | Phlebology2012，271，： | 1 |
| 18 | Molecu- lar actions of prpofol on human 5-HT3A re- ceptors:enhancement as well as inhibition by closely related phenol derivatives 显示文摘 | Barann M Linden I Witten S | 2008 | Anesth&Analg2008，106，3： | 1 |
| 19 | Diffusion-limited aggregation显示文摘 | Witten T A Sander L M | 1983 | Physical Review B1983，27，9： | 1 |
| 20 | Arithmetic Coding for Data Compression显示文摘 | Witten I H Neal R M Cleary J G | 1997 | Communications of the ACM1997，30，6： | 1 |
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