C-type lectin-like receptor 2 specifies a functionally distinct subpopulation within phenotypically defined hematopoietic stem cell population that contribute to emergent megakaryopoiesis
C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts o...
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Veröffentlicht in: | International journal of hematology 2022-03, Vol.115 (3), p.310-321 |
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Sprache: | eng |
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Zusammenfassung: | C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts of megakaryocyte-related molecules than CLEC-2
low
LT-HSCs. Although CLEC-2
high
LT-HSCs had immature clonogenic activity, cultured CLEC-2
high
LT-HSCs preferentially differentiated into megakaryocytes. CLEC-2
high
HSCs yielded 6.8 times more megakaryocyte progenitors (MkPs) and 6.0 times more platelets 2 weeks and 1 week after transplantation compared with CLEC-2
low
LT-HSCs. However, platelet yield from CLEC-2
high
HSCs gradually declined with the loss of MkPs, while CLEC-2
low
HSCs self-renewed long-term, indicating that CLEC-2
high
LT-HSCs mainly contribute to early megakaryopoiesis. Treatment with pI:C and LPS increased the proportion of CLEC-2
high
LT-HSCs within LT-HSCs. Almost all CLEC-2
low
LT-HSCs were in the G0 phase and barely responded to pI:C. In contrast, 54% of CLEC-2
high
LT-HSCs were in G0, and pI:C treatment obliged CLEC-2
high
LT-HSCs to enter the cell cycle and differentiate into megakaryocytes, indicating that CLEC-2
high
LT-HSCs are primed for cell cycle entry and rapidly yield platelets in response to inflammatory stress. In conclusion, CLEC-2
high
LT-HSCs appear to act as a reserve for emergent platelet production under stress conditions. |
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ISSN: | 0925-5710 1865-3774 |
DOI: | 10.1007/s12185-021-03220-9 |