MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors.
Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in those processes and used the poorly understood regulation of megakaryocyte-erythrocyte progenitors (MEPs) in hematopoiesis as a model system. We report here that miR-150 modulates lineage fate in MEPs. Using a novel methodology capable of profiling miRNA expression in small numbers of primary cells, we identify miR-150 as preferentially expressed in the megakaryocytic lineage. Through gain- and loss-of-function experiments, we demonstrate that miR-150 drives MEP differentiation toward megakaryocytes at the expense of erythroid cells in vitro and in vivo. Moreover, we identify the transcription factor MYB as a critical target of miR-150 in this regulation. These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multipotent cells.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jun
J
Lu
Shangqin
S
Guo
Benjamin L
BL
Ebert
Hao
H
Zhang
Xiao
X
Peng
Jocelyn
J
Bosco
Jennifer
J
Pretz
Rita
R
Schlanger
Judy Y
JY
Wang
Raymond H
RH
Mak
David M
DM
Dombkowski
Frederic I
FI
Preffer
David T
DT
Scadden
Todd R
TR
Golub
D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000037:antagonists & inhibitors / Q000235:genetics; D013926:Thrombopoietin / Q000494:pharmacology
D018952:Antigens, CD34; D039661:Integrin beta3; D035683:MicroRNAs; D040201:Platelet Membrane Glycoprotein IIb; D020598:Proto-Oncogene Proteins c-myb; D004921:Erythropoietin; D013926:Thrombopoietin