title: Insulin-InsR signaling drives multipotent progenitor differentiation toward lymphoid lineages.
abstract: The lineage commitment of HSCs generates balanced myeloid and lymphoid populations in hematopoiesis. However, the underlying mechanisms that control this process remain largely unknown. Here, we show that insulin-insulin receptor (InsR) signaling is required for lineage commitment of multipotent progenitors (MPPs). Deletion of Insr in murine bone marrow causes skewed differentiation of MPPs to myeloid cells. mTOR acts as a downstream effector that modulates MPP differentiation. mTOR activates Stat3 by phosphorylation at serine 727 under insulin stimulation, which binds to the promoter of Ikaros, leading to its transcription priming. Our findings reveal that the insulin-InsR signaling drives MPP differentiation into lymphoid lineages in early lymphopoiesis, which is essential for maintaining a balanced immune system for an individual organism.
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Pengyan
authors.initials: P
authors.lastname: Xia
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Guanling
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China fanz@moon.ibp.ac.cn.
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D061385:Insulins / Q000378:metabolism*; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology; D011972:Receptor, Insulin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D061385:Insulins; D050796:STAT3 Transcription Factor; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D011972:Receptor, Insulin; D058570:TOR Serine-Threonine Kinases