イシズ　アヤコ   Ishizu Ayako   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Thrombopoietin Metabolically Primes Hematopoietic Stem Cells to Megakaryocyte-Lineage Differentiation.
掲載誌名	正式名：Cell reports 略　 称：Cell Rep ISSNコード：22111247
掲載区分	国外
巻・号・頁	25(7),pp.1772-1785.e6
著者・共著者	Nakamura-Ishizu Ayako, Matsumura Takayoshi, Stumpf Patrick S, Umemoto Terumasa, Takizawa Hitoshi, Takihara Yuji, O'Neil Aled, Majeed A'Qilah Banu Bte Abdul, MacArthur Ben D, Suda Toshio
発行年月	2018/11
概要	During acute myelosuppression or thrombocytopenia, bone marrow (BM) hematopoietic cells respond rapidly to replenish peripheral blood platelets. While the cytokine thrombopoietin (Thpo) both regulates platelet production and maintains HSC potential, whether Thpo controls megakaryocyte (Mk)-lineage differentiation of HSCs is unclear. Here, we show that Thpo rapidly upregulates mitochondrial activity in HSCs, an activity accompanied by differentiation to an Mk lineage. Moreover, in unperturbed hematopoiesis, HSCs with high mitochondrial activity exhibit Mk-lineage differentiation in vitro and myeloid lineage-biased reconstitution in vivo. Furthermore, Thpo skewed HSCs to express the tetraspanin CD9, a pattern correlated with mitochondrial activity. Mitochondria-active HSCs are resistant to apoptosis and oxidative stress upon Thpo stimulation. Thpo-regulated mitochondrial activity associated with mitochondrial translocation of STAT3 phosphorylated at serine 727. Overall, we report an important role for Thpo in regulating rapid Mk-lineage commitment. Thpo-dependent changes in mitochondrial metabolism prime HSCs to undergo direct differentiation to an Mk lineage.
DOI	10.1016/j.celrep.2018.10.059
PMID	30428347