title: microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia.
abstract: The function of microRNAs (miRNAs) in hematopoietic stem cells (HSCs), committed progenitors, and leukemia stem cells (LSCs) is poorly understood. We show that miR-29a is highly expressed in HSC and down-regulated in hematopoietic progenitors. Ectopic expression of miR-29a in mouse HSC/progenitors results in acquisition of self-renewal capacity by myeloid progenitors, biased myeloid differentiation, and the development of a myeloproliferative disorder that progresses to acute myeloid leukemia (AML). miR-29a promotes progenitor proliferation by expediting G1 to S/G2 cell cycle transitions. miR-29a is overexpressed in human AML and, like human LSC, miR-29a-expressing myeloid progenitors serially transplant AML. Our data indicate that miR-29a regulates early hematopoiesis and suggest that miR-29a initiates AML by converting myeloid progenitors into self-renewing LSC.
authors.affiliation: Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Yoon-Chi
authors.initials: YC
authors.lastname: Han
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Park
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Mofang
authors.initials: M
authors.lastname: Liu
authors.forename: Yongrui
authors.initials: Y
authors.lastname: Zou
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D022423:Myeloid Cells / Q000502:physiology*; D009196:Myeloproliferative Disorders / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs