{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:29:48Z","timestamp":1787239788250,"version":"build-2736575974"},"reference-count":87,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR055580"],"award-info":[{"award-number":["R01 AR055580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG003988"],"award-info":[{"award-number":["R01HG003988"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["grant No. 345\/16"],"award-info":[{"award-number":["grant No. 345\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001658","name":"Minerva Foundation","doi-asserted-by":"publisher","award":["grant No. 713533"],"award-info":[{"award-number":["grant No. 713533"]}],"id":[{"id":"10.13039\/501100001658","id-type":"DOI","asserted-by":"publisher"}]},{"name":"David and Fela Shapell Family Center for Genetic Disorders"},{"name":"Estate of Mr. and Mrs. van Adelsberge"},{"DOI":"10.13039\/100005595","name":"University of California","doi-asserted-by":"publisher","award":["DEAC02-05CH11231"],"award-info":[{"award-number":["DEAC02-05CH11231"]}],"id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PCEFP3_186993"],"award-info":[{"award-number":["PCEFP3_186993"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The mechanical challenge of attaching elastic tendons to stiff bones is solved by the formation of a unique transitional tissue. Here, we show that murine tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, under regulation of shared regulatory elements and Kr\u00fcppel-like factors (KLFs) transcription factors. High-throughput bulk and single-cell RNA sequencing of humeral attachment cells revealed expression of hundreds of chondrogenic and tenogenic genes, which was validated by in situ hybridization and single-molecule ISH. ATAC sequencing showed that attachment cells share accessible intergenic chromatin areas with either tenocytes or chondrocytes. Epigenomic analysis revealed enhancer signatures for most of these regions. Transgenic mouse enhancer reporter assays verified the shared activity of some of these enhancers. Finally, integrative chromatin and motif analyses and transcriptomic data implicated KLFs as regulators of attachment cells. Indeed, blocking expression of both\n                    <jats:italic>Klf2<\/jats:italic>\n                    and\n                    <jats:italic>Klf4<\/jats:italic>\n                    in developing limb mesenchyme impaired their differentiation.\n                  <\/jats:p>","DOI":"10.7554\/elife.55361","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T07:00:56Z","timestamp":1610694056000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.55361","source":"Crossref","is-referenced-by-count":58,"title":["Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8216-2908","authenticated-orcid":true,"given":"Shiri","family":"Kult","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsviya","family":"Olender","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1969-2313","authenticated-orcid":true,"given":"Marco","family":"Osterwalder","sequence":"additional","affiliation":[{"name":"Environmental Genomics and Systems Biology Division, Lawrence Berkeley National, Berkeley, United States"},{"name":"Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetalana","family":"Markman","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena","family":"Leshkowitz","sequence":"additional","affiliation":[{"name":"Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Krief","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Blecher-Gonen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shani","family":"Ben-Moshe","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-5078","authenticated-orcid":true,"given":"Lydia","family":"Farack","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Keren-Shaul","sequence":"additional","affiliation":[{"name":"Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomer-Meir","family":"Salame","sequence":"additional","affiliation":[{"name":"Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-8478","authenticated-orcid":true,"given":"Terence D","family":"Capellini","sequence":"additional","affiliation":[{"name":"Department of Human Evolutionary Biology, Harvard University, Department of Human Evolutionary Biology, United States; Broad Institute of Harvard and MIT, Cambridge, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-2522","authenticated-orcid":true,"given":"Shalev","family":"Itzkovitz","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Amit","sequence":"additional","affiliation":[{"name":"Department of Immunology, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4130-7784","authenticated-orcid":true,"given":"Axel","family":"Visel","sequence":"additional","affiliation":[{"name":"Environmental Genomics and Systems Biology Division, Lawrence Berkeley National, Berkeley, United States"},{"name":"U.S. Department of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, United States"},{"name":"School of Natural Sciences, University of California, Merced, Merced, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-6602","authenticated-orcid":true,"given":"Elazar","family":"Zelzer","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.neuron.2017.04.022","article-title":"The dynamic epigenetic landscape of the retina during development, reprogramming, and tumorigenesis","volume":"94","author":"Aldiri","year":"2017","journal-title":"Neuron"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1101\/gr.213066.116","article-title":"Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding","volume":"27","author":"Andrey","year":"2017","journal-title":"Genome Research"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/jcb.240460410","article-title":"Developmental expression and hormonal regulation of the rat matrix gla protein (MGP) gene in chondrogenesis and osteogenesis","volume":"46","author":"Barone","year":"1991","journal-title":"Journal of Cellular Biochemistry"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1215\/S1152851705000232","article-title":"The role of pericytes in blood-vessel formation and maintenance","volume":"7","author":"Bergers","year":"2005","journal-title":"Neuro-Oncology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1002\/gene.20026","article-title":"Laser capture microdissection of fluorescently labeled embryonic cranial neural crest cells","volume":"39","author":"Bhattacherjee","year":"2004","journal-title":"Genesis"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.devcel.2009.10.010","article-title":"Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the Tendon-Skeleton junction","volume":"17","author":"Blitz","year":"2009","journal-title":"Developmental Cell"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1242\/dev.093906","article-title":"Tendon-bone attachment unit is formed modularly by a distinct pool of scx- and Sox9-positive progenitors","volume":"140","author":"Blitz","year":"2013","journal-title":"Development"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/0471142727.mb2129s109","article-title":"ATAC-seq: a method for assaying chromatin accessibility Genome-Wide","volume":"109","author":"Buenrostro","year":"2015","journal-title":"Current Protocols in Molecular Biology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nature Biotechnology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"D762","DOI":"10.1093\/nar\/gkx1020","article-title":"The UCSC genome browser database: 2018 update","volume":"46","author":"Casper","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110928","article-title":"Cdx2 animal models reveal developmental origins of cancers","volume":"10","author":"Chawengsaksophak","year":"2019","journal-title":"Genes"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-13-40","article-title":"The Kr\u00fcppel-like factor 2 and Kr\u00fcppel-like factor 4 genes interact to maintain endothelial integrity in mouse embryonic vasculogenesis","volume":"13","author":"Chiplunkar","year":"2013","journal-title":"BMC Developmental Biology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/S1357-2725(00)00059-5","article-title":"The biology of the mammalian Kr\u00fcppel-like family of transcription factors","volume":"32","author":"Dang","year":"2000","journal-title":"The International Journal of Biochemistry & Cell Biology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.mod.2018.05.002","article-title":"Genetic interaction between Gli3 and Ezh2 during limb pattern formation","volume":"151","author":"Deimling","year":"2018","journal-title":"Mechanisms of Development"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S0002-9440(10)63002-7","article-title":"\u00a0Endothelial KLF2\u00a0links local arterial shear stress levels to the expression of vascular tone-regulating genes","volume":"167","author":"Dekker","year":"2005","journal-title":"The American Journal of Pathology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ydbio.2015.06.020","article-title":"Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis","volume":"405","author":"Dyment","year":"2015","journal-title":"Developmental Biology"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-48","article-title":"GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists","volume":"10","author":"Eden","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"ENCODE Project Consortium","year":"2012","journal-title":"Nature"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1242\/dev.167882","article-title":"Bone morphology is regulated modularly by global and regional genetic programs","volume":"146","author":"Eyal","year":"2019","journal-title":"Development"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165381","article-title":"Development of migrating tendon-bone attachments involves replacement of progenitor populations","volume":"145","author":"Felsenthal","year":"2018","journal-title":"Development"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.2106\/00004623-200402000-00002","article-title":"The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears","volume":"86","author":"Galatz","year":"2004","journal-title":"The Journal of Bone & Joint Surgery"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.bpj.2009.05.043","article-title":"Functional grading of mineral and collagen in the attachment of tendon to bone","volume":"97","author":"Genin","year":"2009","journal-title":"Biophysical Journal"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29329","article-title":"Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height","volume":"6","author":"Guo","year":"2017","journal-title":"eLife"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"982","DOI":"10.2106\/00004623-199173070-00004","article-title":"Repairs of the rotator cuff. Correlation of functional results with integrity of the cuff","volume":"73","author":"Harryman","year":"1991","journal-title":"The Journal of Bone & Joint Surgery"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Molecular Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1101\/gr.121145.111","article-title":"Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1","volume":"21","author":"Hu","year":"2011","journal-title":"Genome Research"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/ncb2384","article-title":"Single-molecule transcript counting of stem-cell markers in the mouse intestine","volume":"14","author":"Itzkovitz","year":"2012","journal-title":"Nature Cell Biology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1126\/science.1247651","article-title":"Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types","volume":"343","author":"Jaitin","year":"2014","journal-title":"Science"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/ncb1698","article-title":"A core klf circuitry regulates self-renewal of embryonic stem cells","volume":"10","author":"Jiang","year":"2008","journal-title":"Nature Cell Biology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nn.3980","article-title":"Single-cell analysis reveals transcriptional heterogeneity of neural progenitors in human cortex","volume":"18","author":"Johnson","year":"2015","journal-title":"Nature Neuroscience"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/S0092-8674(00)80364-5","article-title":"Molecular models for vertebrate limb development","volume":"90","author":"Johnson","year":"1997","journal-title":"Cell"},{"key":"bib33","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1242\/dev.129.11.2619","article-title":"The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the Colon","volume":"129","author":"Katz","year":"2002","journal-title":"Development"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1038\/s41596-019-0164-4","article-title":"MARS-seq2.0: an experimental and analytical pipeline for indexed sorting combined with single-cell RNA sequencing","volume":"14","author":"Keren-Shaul","year":"2019","journal-title":"Nature Protocols"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1126\/science.277.5334.1986","article-title":"LKLF: a transcriptional regulator of single-positive T cell quiescence and survival","volume":"277","author":"Kuo","year":"1997","journal-title":"Science"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2020.02.031","article-title":"Comprehensive in\u00a0Vivo Interrogation Reveals Phenotypic Impact of Human Enhancer Variants","volume":"180","author":"Kvon","year":"2020","journal-title":"Cell"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1186\/s13040-014-0034-0","article-title":"Performance of genetic programming optimised Bowtie2 on genome comparison and analytic testing (GCAT) benchmarks","volume":"8","author":"Langdon","year":"2015","journal-title":"BioData Mining"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.stem.2014.05.006","article-title":"Chromatin repressive complexes in stem cells, development, and Cancer","volume":"14","author":"Laugesen","year":"2014","journal-title":"Cell Stem Cell"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.devcel.2006.09.006","article-title":"Klf2 is an essential regulator of vascular hemodynamic forces in vivo","volume":"11","author":"Lee","year":"2006","journal-title":"Developmental Cell"},{"key":"bib40","first-page":"30","article-title":"The incidence of full thickness rotator cuff tears in a large cadaveric population","volume":"54","author":"Lehman","year":"1995","journal-title":"Bulletin (Hospital for Joint Diseases"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/0092-8674(95)90492-1","article-title":"A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis","volume":"80","author":"Li","year":"1995","journal-title":"Cell"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1001\/archopht.125.4.523","article-title":"The eyelid margin: a transitional zone for 2 epithelial phenotypes","volume":"125","author":"Liu","year":"2007","journal-title":"Archives of Ophthalmology"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1115\/1.4002641","article-title":"Mechanisms of bimaterial attachment at the interface of tendon to bone","volume":"133","author":"Liu","year":"2011","journal-title":"Journal of Engineering Materials and Technology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.mechmat.2011.08.005","article-title":"Bi-material attachment through a compliant interfacial system at the tendon-to-bone insertion site","volume":"44","author":"Liu","year":"2012","journal-title":"Mechanics of Materials"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1089\/ten.tea.2011.0338","article-title":"Spatial and temporal expression of molecular markers and cell signals during normal development of the mouse patellar tendon","volume":"18","author":"Liu","year":"2012","journal-title":"Tissue Engineering Part A"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065411","article-title":"A role for hedgehog signaling in the differentiation of the insertion site of the patellar tendon in the mouse","volume":"8","author":"Liu","year":"2013","journal-title":"PLOS ONE"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.1242\/dev.163519","article-title":"Molecular analysis of enthesopathy in a mouse model of hypophosphatemic rickets","volume":"145","author":"Liu","year":"2018","journal-title":"Development"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/gene.10092","article-title":"Expression of cre recombinase in the developing mouse limb bud driven by a prxl enhancer","volume":"33","author":"Logan","year":"2002","journal-title":"Genesis"},{"key":"bib49","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1146\/annurev-bioeng-071910-124656","article-title":"Functional attachment of soft tissues to bone: development, healing, and tissue engineering","volume":"15","author":"Lu","year":"2013","journal-title":"Annual Review of Biomedical Engineering"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1662-y","article-title":"EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data","volume":"20","author":"Lun","year":"2019","journal-title":"Genome Biology"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1038\/nprot.2013.109","article-title":"Single-molecule mRNA detection and counting in mammalian tissue","volume":"8","author":"Lyubimova","year":"2013","journal-title":"Nature Protocols"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nature Neuroscience"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nrgastro.2014.181","article-title":"Barrett oesophagus: lessons on its origins from the lesion itself","volume":"12","author":"McDonald","year":"2015","journal-title":"Nature Reviews Gastroenterology & Hepatology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"McLean","year":"2010","journal-title":"Nature Biotechnology"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.yexcr.2011.12.013","article-title":"Kr\u00fcppel-like factor 4 regulates membranous and endochondral ossification","volume":"318","author":"Michikami","year":"2012","journal-title":"Experimental Cell Research"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1002\/dvdy.20892","article-title":"Kinetics of tamoxifen-regulated cre activity in mice using a cartilage-specific CreER(T) to assay temporal activity windows along the proximodistal limb skeleton","volume":"235","author":"Nakamura","year":"2006","journal-title":"Developmental Dynamics"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1242\/dev.161208","article-title":"Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors","volume":"145","author":"Orgeur","year":"2018","journal-title":"Development"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<145::AID-GENE14>3.0.CO;2-C","article-title":"Col2a1-directed expression of cre recombinase in differentiating chondrocytes in transgenic mice","volume":"26","author":"Ovchinnikov","year":"2000","journal-title":"Genesis"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1002\/dvdy.23861","article-title":"Molecular profiling of synovial joints: use of microarray analysis to identify factors that direct the development of the knee and elbow","volume":"241","author":"Pazin","year":"2012","journal-title":"Developmental Dynamics"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1002\/dvdy.21179","article-title":"Generation of transgenic tendon reporters, ScxGFP and ScxAP, using regulatory elements of the scleraxis gene","volume":"236","author":"Pryce","year":"2007","journal-title":"Developmental Dynamics"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/0471250953.bi1112s47","article-title":"BEDTools: the Swiss-Army tool for genome feature analysis","volume":"47","author":"Quinlan","year":"2014","journal-title":"Current Protocols in Bioinformatics"},{"key":"bib63","article-title":"R: A language and environment for statistical computing","author":"R Development Core Team","year":"2013","unstructured":"R Development Core Team. 2013. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. http:\/\/www.R-project.org."},{"key":"bib64","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/nmeth.1253","article-title":"Imaging individual mRNA molecules using multiple singly labeled probes","volume":"5","author":"Raj","year":"2008","journal-title":"Nature Methods"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/0092-8674(93)90626-2","article-title":"Sonic hedgehog mediates the polarizing activity of the ZPA","volume":"75","author":"Riddle","year":"1993","journal-title":"Cell"},{"key":"bib66","doi-asserted-by":"publisher","DOI":"10.1242\/dev.170241","article-title":"FGF signaling patterns cell fate at the interface between tendon and bone","volume":"146","author":"Roberts","year":"2019","journal-title":"Development"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00441-004-1005-4","article-title":"Differentiation of epithelial cells in the urinary tract","volume":"320","author":"Romih","year":"2005","journal-title":"Cell and Tissue Research"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1016\/j.yexcr.2011.07.011","article-title":"Boundaries, junctions and transitions in the gastrointestinal tract","volume":"317","author":"San Roman","year":"2011","journal-title":"Experimental Cell Research"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1242\/dev.112714","article-title":"Enthesis fibrocartilage cells originate from a population of Hedgehog-responsive cells modulated by the loading environment","volume":"142","author":"Schwartz","year":"2015","journal-title":"Development"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1242\/dev.139303","article-title":"Enthesis regeneration: a role for Gli1+ progenitor cells","volume":"144","author":"Schwartz","year":"2017","journal-title":"Development"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/11926","article-title":"Klf4 is a transcription factor required for establishing the barrier function of the skin","volume":"22","author":"Segre","year":"1999","journal-title":"Nature Genetics"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"18504","DOI":"10.1074\/jbc.272.29.18504","article-title":"Two potent nuclear localization signals in the Gut-enriched Kr\u00fcppel-like factor define a subfamily of closely related kr\u00fcppel proteins","volume":"272","author":"Shields","year":"1997","journal-title":"Journal of Biological Chemistry"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-1-62703-989-5_15","article-title":"Nonradioactive in situ hybridization on skeletal tissue sections","volume":"1130","author":"Shwartz","year":"2014","journal-title":"Methods in Molecular Biology"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/dvg.20667","article-title":"Sox9-expressing precursors are the cellular origin of the cruciate ligament of the knee joint and the limb tendons","volume":"48","author":"Soeda","year":"2010","journal-title":"Genesis"},{"key":"bib76","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9536","article-title":"Spatiotemporal structure of cell fate decisions in murine neural crest","volume":"364","author":"Soldatov","year":"2019","journal-title":"Science"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"PNAS"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1242\/dev.096354","article-title":"Scx+\/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon\/ligament","volume":"140","author":"Sugimoto","year":"2013","journal-title":"Development"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"7902","DOI":"10.1073\/pnas.1019507108","article-title":"Site-specific integrase-mediated transgenesis in mice via pronuclear injection","volume":"108","author":"Tasic","year":"2011","journal-title":"PNAS"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0736-0266(03)0057-3","article-title":"Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site","volume":"21","author":"Thomopoulos","year":"2003","journal-title":"Journal of Orthopaedic Research"},{"key":"bib82","first-page":"35","article-title":"The development and morphogenesis of the tendon-to-bone insertion - what development can teach us about healing","volume":"10","author":"Thomopoulos","year":"2010","journal-title":"Journal of Musculoskeletal & Neuronal Interactions"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/nprot.2009.230","article-title":"Expander: from expression microarrays to networks and functions","volume":"5","author":"Ulitsky","year":"2010","journal-title":"Nature Protocols"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.bbrc.2009.12.002","article-title":"Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells","volume":"391","author":"Villarreal","year":"2010","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"},{"key":"bib86","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biology"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.cell.2012.12.033","article-title":"Genome-wide chromatin state transitions associated with developmental and environmental cues","volume":"152","author":"Zhu","year":"2013","journal-title":"Cell"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/55361\/elife-55361-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/55361\/elife-55361-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/55361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:59:20Z","timestamp":1697057960000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/55361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,15]]},"references-count":87,"alternative-id":["10.7554\/eLife.55361"],"URL":"https:\/\/doi.org\/10.7554\/elife.55361","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"accession","id":"ENCSR905FFU","asserted-by":"subject"},{"id-type":"accession","id":"ENCSR426EZM","asserted-by":"subject"},{"id-type":"accession","id":"ENCSR416OYH","asserted-by":"subject"},{"id-type":"accession","id":"ENCSR022DED","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE144306","asserted-by":"subject"},{"id-type":"accession","id":"GSE160090","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.55361.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.739372514.793582860","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.55361.sa1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.01.29.924654","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,15]]},"article-number":"e55361"}}