C-type lectin-like receptor 2 specifies a functionally distinct subpopulation within phenotypically defined hematopoietic stem cell population that contribute to emergent megakaryopoiesis.

Takahiro Kumode, Hirokazu Tanaka, Jorge Luis Esipinoza, Shinya Rai, Yasuhiro Taniguchi, Ryosuke Fujiwara, Keigo Sano, Kentaro Serizawa, Yoshio Iwata, Yasuyoshi Morita, Itaru Matsumura

International journal of hematology 2022 Mar

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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-2low LT-HSCs. Although CLEC-2high LT-HSCs had immature clonogenic activity, cultured CLEC-2high LT-HSCs preferentially differentiated into megakaryocytes. CLEC-2high 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-2low LT-HSCs. However, platelet yield from CLEC-2high HSCs gradually declined with the loss of MkPs, while CLEC-2low HSCs self-renewed long-term, indicating that CLEC-2high LT-HSCs mainly contribute to early megakaryopoiesis. Treatment with pI:C and LPS increased the proportion of CLEC-2high LT-HSCs within LT-HSCs. Almost all CLEC-2low LT-HSCs were in the G0 phase and barely responded to pI:C. In contrast, 54% of CLEC-2high LT-HSCs were in G0, and pI:C treatment obliged CLEC-2high LT-HSCs to enter the cell cycle and differentiate into megakaryocytes, indicating that CLEC-2high LT-HSCs are primed for cell cycle entry and rapidly yield platelets in response to inflammatory stress. In conclusion, CLEC-2high LT-HSCs appear to act as a reserve for emergent platelet production under stress conditions. © 2022. Japanese Society of Hematology.

Citation

Takahiro Kumode, Hirokazu Tanaka, Jorge Luis Esipinoza, Shinya Rai, Yasuhiro Taniguchi, Ryosuke Fujiwara, Keigo Sano, Kentaro Serizawa, Yoshio Iwata, Yasuyoshi Morita, Itaru Matsumura. C-type lectin-like receptor 2 specifies a functionally distinct subpopulation within phenotypically defined hematopoietic stem cell population that contribute to emergent megakaryopoiesis. International journal of hematology. 2022 Mar;115(3):310-321