title: Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin.
abstract: Tissue homeostasis demands regulatory feedback, suggesting that hematopoietic stem cell (HSC) activity is controlled in part by HSC progeny. Yet, cell extrinsic HSC regulation has been well characterized only in niche cells of non-hematopoietic origin. Here we identify feedback regulation of HSCs by megakaryocytes (Mks), which are mature hematopoietic cells, through production of thrombopoietin (Thpo), a cytokine pertinent for HSC maintenance. Induced ablation of Mk cell population in mice perturbed quiescent HSCs in bone marrow (BM). The ablation of Mks resulted in decreased intra-BM Thpo concentration presumably due to Thpo production by Mks. Thpo administration Mk ablated mice restored HSC functions. Overall, our study establishes Mk as an essential cellular component of the HSC niche and delineates cytokine-oriented regulation of HSCs by their own progeny.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakamura-Ishizu
authors.forename: Keiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Masato
authors.initials: M
authors.lastname: Fujioka
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D002454:Cell Differentiation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche; D013926:Thrombopoietin / Q000378:metabolism*
chemical_list: D013926:Thrombopoietin