{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:12:21Z","timestamp":1788174741711,"version":"build-2803163510"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91540108"],"award-info":[{"award-number":["91540108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tsinghua-Peking Center for Life Sciences"},{"name":"Chunfeng Fund","award":["2021Z99CFY020"],"award-info":[{"award-number":["2021Z99CFY020"]}]},{"DOI":"10.13039\/501100004147","name":"Tsinghua University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transforming growth factor \u03b2 (TGF-\u03b2) superfamily proteins are potent regulators of cellular development and differentiation. Nodal\/Activin\/TGF-\u03b2 and BMP ligands are both present in the intra- and extracellular milieu during early development, and cross-talk between these two branches of developmental signaling is currently the subject of intense research focus. Here, we show that the\u00a0Nodal\u00a0induced\u00a0lncRNA-Smad7\u00a0regulates cell fate determination via repression of BMP signaling in mouse embryonic stem cells (mESCs). Depletion of lncRNA-Smad7 dramatically impairs cardiomyocyte differentiation in mESCs. Moreover, lncRNA-Smad7 represses Bmp2 expression through binding with the Bmp2 promoter region via (CA)12-repeats that forms an R-loop. Importantly, Bmp2 knockdown rescues defects in cardiomyocyte differentiation induced by lncRNA-Smad7 knockdown. Hence, lncRNA-Smad7 antagonizes BMP signaling in mESCs, and similarly regulates cell fate determination between osteocyte and myocyte formation in C2C12 mouse myoblasts. Moreover, lncRNA-Smad7 associates with hnRNPK in mESCs and hnRNPK binds at the Bmp2 promoter, potentially contributing to Bmp2 expression repression. The antagonistic effects between Nodal\/TGF-\u03b2 and BMP signaling via lncRNA-Smad7 described in this work provides a framework for understanding cell fate determination in early development.<\/jats:p>","DOI":"10.1093\/nar\/gkac780","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T10:40:03Z","timestamp":1663843203000},"page":"10526-10543","source":"Crossref","is-referenced-by-count":18,"title":["<i>LncRNA-Smad7<\/i>mediates cross-talk between Nodal\/TGF-\u03b2 and BMP signaling to regulate cell fate determination of pluripotent and multipotent cells"],"prefix":"10.1093","volume":"50","author":[{"given":"Xiaohui","family":"Kong","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yan","sequence":"additional","affiliation":[{"name":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pujuan","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Fu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyao","family":"Sun","sequence":"additional","affiliation":[{"name":"Joint Graduate Program of Peking-Tsinghua-NIBS, Tsinghua University , Beijing \u00a0100084,\u00a0 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-4700","authenticated-orcid":false,"given":"Junbiao","family":"Dai","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen \u00a0518055,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangfeng Cliff","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 China"},{"name":"MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-jie Gogo","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University , Beijing \u00a0100084,\u00a0 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7496-4131","authenticated-orcid":false,"given":"Qiaoran","family":"Xi","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University , Beijing \u00a0100084,\u00a0 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