microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia.
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.
Han
Yoon-Chi
YC
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Park
Christopher Y
CY
Bhagat
Govind
G
Zhang
Jinping
J
Wang
Yulei
Y
Fan
Jian-Bing
JB
Liu
Mofang
M
Zou
Yongrui
Y
Weissman
Irving L
IL
Gu
Hua
H
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
C532045:MIRN29a microRNA, human; D035683:MicroRNAs