High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production.

Autor: Heazlewood SY; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Ahmad T; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Cao B; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Cao H; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Domingues M; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Sun X; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Heazlewood CK; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Li S; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Williams B; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., Fulton M; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia., White JF; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia., Nebl T; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia., Nefzger CM; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia.; Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia., Polo JM; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia.; Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia.; Monash Biomedicine Discovery Institute, Melbourne, VIC, Australia., Kile BT; Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia., Kraus F; Monash Biomedicine Discovery Institute, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia., Ryan MT; Monash Biomedicine Discovery Institute, Melbourne, VIC, Australia.; Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia., Sun YB; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia.; Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia.; Monash Biomedicine Discovery Institute, Melbourne, VIC, Australia., Choong PFM; Department of Surgery, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.; Bone and Soft Tissue Sarcoma Service, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Department of Orthopaedics, St. Vincent's Hospital Melbourne, Melbourne, VIC, Australia., Ellis SL; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia., Anko ML; Centre for Reproductive Health and Centre for Cancer Research, Hudson Institute of Medical Research, Melbourne, VIC, Australia.; Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Nilsson SK; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organization, Melbourne, VIC, Australia. susie.nilsson@csiro.au.; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, Australia. susie.nilsson@csiro.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 13; Vol. 14 (1), pp. 2099. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1038/s41467-023-37780-7
Abstrakt: Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3 Δ/Δ ) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe thrombocytopenia is observed in animals with diminished LCM, although there is no change in MK ploidy distribution, uncoupling endoreduplication and platelet production. When HSC isolated from a microenvironment essentially devoid of LCM reconstitute hematopoiesis in lethally irradiated mice, the absence of LCM increases HSC in BM, blood and spleen, and the recapitulation of thrombocytopenia. In contrast, following a competitive transplant using minimal numbers of WT HSC together with HSC from a microenvironment with diminished LCM, sufficient WT HSC-generated LCM regulates a normal HSC pool and prevents thrombocytopenia. Importantly, LCM are conserved in humans.
(© 2023. Crown.)
Databáze: MEDLINE
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