Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration
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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; Nerlov, Claus; Weischenfeldt, Joachim; Reckzeh, Kristian; Theilgaard-Mönch, Kim.
In: Cell Reports, Vol. 43, No. 7, 114475, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Endomucin marks quiescent long-term multi-lineage repopulating hematopoietic stem cells and is essential for their transendothelial migration
AU - Engelhard, Sophia
AU - Estruch, Montserrat
AU - Qin, Shuyu
AU - Engelhard, Christoph A.
AU - Rodriguez-Gonzalez, Francisco G.
AU - Drilsvik, Martine
AU - Martin-Gonzalez, Javier
AU - Lu, Jeng Wei
AU - Bryder, David
AU - Nerlov, Claus
AU - Weischenfeldt, Joachim
AU - Reckzeh, Kristian
AU - Theilgaard-Mönch, Kim
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - bone marrow niche
KW - CP: Stem cell research
KW - cross-species HSC marker
KW - endomucin
KW - endothelial cells
KW - hematopoietic stem cell
KW - mobilization
KW - transplantation
U2 - 10.1016/j.celrep.2024.114475
DO - 10.1016/j.celrep.2024.114475
M3 - Journal article
C2 - 38996072
AN - SCOPUS:85198069529
VL - 43
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 7
M1 - 114475
ER -
ID: 399235369