{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:36:11Z","timestamp":1786390571759,"version":"build-2736575974"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Transforming growth factor-\u03b2 (TGF-\u03b2) signaling plays a crucial role in maintaining the quiescence and self-renewal potential of hematopoietic stem cells (HSCs). Despite decades of research, the underlying mechanisms of TGF-\u03b2 signaling in HSCs remain elusive due to conflicting phenotypes of various knockout (KO) mouse models. Here, we show that HSCs co-express\n                      <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Tgfbr3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Endoglin (Eng<\/jats:italic>\n                      ) but rarely express\n                      <jats:italic toggle=\"yes\">Tgfbr1<\/jats:italic>\n                      , whereas lymphocytes co-express\n                      <jats:italic toggle=\"yes\">Tgfbr1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                      but rarely express\n                      <jats:italic toggle=\"yes\">Tgfbr3<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">Eng<\/jats:italic>\n                      . We also demonstrate that\n                      <jats:italic toggle=\"yes\">Tgfbr3<\/jats:italic>\n                      is dispensable for the maintenance of immune homeostasis, in contrast to\n                      <jats:italic toggle=\"yes\">Tgfbr1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                      , either of which is essential for lymphocyte homeostasis. Serial transplantation assays revealed that deletion of\n                      <jats:italic toggle=\"yes\">Tgfbr3<\/jats:italic>\n                      in HSCs had little effect on short-term reconstitution but impaired long-term self-renewal potential, a similar phenotype observed in\n                      <jats:italic toggle=\"yes\">Eng<\/jats:italic>\n                      conditional KO mice. Therefore, we propose that lymphocytes rely on the Tgfbr1\/Tgfbr2 complex as suggested by the classical model, whereas HSCs require the unique Tgfbr2\/Tgfbr3\/Eng complex to orchestrate TGF-\u03b2 signaling. Collectively, this study reveals Tgfbr3 as a critical regulator in the maintenance of HSC self-renewal potential and suggests a novel TGF-\u03b2 receptor complex specific to HSCs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/bs9.0000000000000307","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:00:25Z","timestamp":1786388425000},"page":"e00307","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Tgfbr3 is required for the long-term maintenance of self-renewal potential in murine hematopoietic stem cells"],"prefix":"10.1097","volume":"8","author":[{"given":"Xialin","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitai","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglei","family":"Zhai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Ema","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China"},{"name":"Tianjin Institutes of Health Science, Tianjin 301600, China"},{"name":"Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"R1-20260810","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1073\/pnas.96.6.3120","article-title":"In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells.","volume":"96","author":"Cheshier","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R2-20260810","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.cell.2008.10.048","article-title":"Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and 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