| Autor: |
Sophia Engelhard, Montserrat Estruch, Shuyu Qin, Christoph A. Engelhard, Francisco G. Rodriguez-Gonzalez, Martine Drilsvik, Javier Martin-Gonzalez, Jeng-Wei Lu, David Bryder, Claus Nerlov, Joachim Weischenfeldt, Kristian Reckzeh, Kim Theilgaard-Mönch |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 43, Iss 7, Pp 114475- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114475 |
| Popis: |
Summary: Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN+ long-term repopulating HSCs (LT-HSCs; CD150+CD48−LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN− LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN+ LT-HSCs were more quiescent compared to EMCN− LT-HSCs. Emcn−/− and Emcn+/+ mice displayed comparable steady-state hematopoiesis, as well as frequencies, transcriptional programs, and long-term multi-lineage repopulating capacity of their LT-HSCs. Complementary functional analyses further revealed increased cell cycle entry upon treatment with 5-fluorouracil and reduced granulocyte colony-stimulating factor (GCSF) mobilization of Emcn−/− LT-HSCs, demonstrating that EMCN expression by LT-HSCs associates with quiescence in response to hematopoietic stress and is indispensable for effective LT-HSC mobilization. Transplantation of wild-type bone marrow cells into Emcn−/− or Emcn+/+ recipients demonstrated that EMCN is essential for endothelial cell-dependent maintenance/self-renewal of the LT-HSC pool and sustained blood cell production post-transplant. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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