TY - JOUR
T1 - Megakaryocytes are essential for HSC quiescence through the production of thrombopoietin
AU - Nakamura-Ishizu, Ayako
AU - Takubo, Keiyo
AU - Fujioka, Masato
AU - Suda, Toshio
N1 - Funding Information:
The authors thank T. Muraki and T. Hirose for technical assistance. A.N-I. was supported in part by a fellowship from JSPS , Grants-in-Aid for JSPS Fellows (25-40030 and 05-045-0166/4096) a research grant from the SENSHIN medical research foundation , a research grant from the Takeda Foundation and a grant from the Naito Foundation . K. T. was supported in part by a MEXT Grant-in-Aid for Young Scientists (A), a Grant of National Center for Global Health and Medicine and a research grant from the Astellas Foundation for Research on Metabolic Disorders. T.S. and K.T were supported in part by a MEXT Grant-in-Aid for Scientific Research (A) and a MEXT Grant-in-Aid for Scientific Research on Innovative Areas.
Publisher Copyright:
© 2014 The Authors. Published by Elsevier Inc.
PY - 2014/11/14
Y1 - 2014/11/14
N2 - 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.
AB - 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.
KW - Bone marrow
KW - Hematopoietic stem cells
KW - Megakaryocytes
KW - Niche
KW - Thrombopoietin
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U2 - 10.1016/j.bbrc.2014.10.095
DO - 10.1016/j.bbrc.2014.10.095
M3 - Article
C2 - 25451253
AN - SCOPUS:84909999815
SN - 0006-291X
VL - 454
SP - 353
EP - 357
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -