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Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration

Engelhard, Sophia ; Estruch, Montserrat ; Qin, Shuyu ; Engelhard, Christoph A. ; Rodriguez-Gonzalez, Francisco G. ; Drilsvik, Martine ; Martin-Gonzalez, Javier ; Lu, Jeng Wei ; Bryder, David LU and Nerlov, Claus , et al. (2024) In Cell Reports 43(7).
Abstract

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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
bone marrow niche, CP: Stem cell research, cross-species HSC marker, endomucin, endothelial cells, hematopoietic stem cell, mobilization, transplantation
in
Cell Reports
volume
43
issue
7
article number
114475
publisher
Cell Press
external identifiers
  • pmid:38996072
  • scopus:85198069529
ISSN
2211-1247
DOI
10.1016/j.celrep.2024.114475
language
English
LU publication?
yes
id
43c3f8e0-a3c3-4f6a-beca-19aab315feea
date added to LUP
2024-09-24 09:43:26
date last changed
2024-10-08 13:30:25
@article{43c3f8e0-a3c3-4f6a-beca-19aab315feea,
  abstract     = {{<p>Endomucin (EMCN) currently represents the only hematopoietic stem cell (HSC) marker expressed by both murine and human HSCs. Here, we report that EMCN<sup>+</sup> long-term repopulating HSCs (LT-HSCs; CD150<sup>+</sup>CD48<sup>−</sup>LSK) have a higher long-term multi-lineage repopulating capacity compared to EMCN<sup>−</sup> LT-HSCs. Cell cycle analyses and transcriptional profiling demonstrated that EMCN<sup>+</sup> LT-HSCs were more quiescent compared to EMCN<sup>−</sup> LT-HSCs. Emcn<sup>−/−</sup> and Emcn<sup>+/+</sup> 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<sup>−/−</sup> 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<sup>−/−</sup> or Emcn<sup>+/+</sup> 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.</p>}},
  author       = {{Engelhard, Sophia and Estruch, Montserrat and Qin, Shuyu and Engelhard, Christoph A. and Rodriguez-Gonzalez, Francisco G. and Drilsvik, Martine and Martin-Gonzalez, Javier and Lu, Jeng Wei and Bryder, David and Nerlov, Claus and Weischenfeldt, Joachim and Reckzeh, Kristian and Theilgaard-Mönch, Kim}},
  issn         = {{2211-1247}},
  keywords     = {{bone marrow niche; CP: Stem cell research; cross-species HSC marker; endomucin; endothelial cells; hematopoietic stem cell; mobilization; transplantation}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2024.114475}},
  doi          = {{10.1016/j.celrep.2024.114475}},
  volume       = {{43}},
  year         = {{2024}},
}