MiR-24 Is Required for Hematopoietic Differentiation of Mouse Embryonic Stem Cells

Lynn Roy, Emmanuel Bikorimana, Danica Lapid, Hyewon Choi, Tan Nguyen, Richard Dahl

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Overexpression of miRNA, miR-24, in mouse hematopoietic progenitors increases monocytic/ granulocytic differentiation and inhibits B cell development. To determine if endogenous miR-24 is required for hematopoiesis, we antagonized miR-24 in mouse embryonic stem cells (ESCs) and performed in vitro differentiations. Suppression of miR-24 resulted in an inability to produce blood and hematopoietic progenitors (HPCs) from ESCs. The phenotype is not a general defect in mesoderm production since we observe production of nascent mesoderm as well as mesoderm derived cardiac muscle and endothelial cells. Results from blast colony forming cell (BL-CFC) assays demonstrate that miR-24 is not required for generation of the hemangioblast, the mesoderm progenitor that gives rise to blood and endothelial cells. However, expression of the transcription factors Runx1 and Scl is greatly reduced, suggesting an impaired ability of the hemangioblast to differentiate. Lastly, we observed that known miR-24 target, Trib3, is upregulated in the miR-24 antagonized embryoid bodies (EBs). Overexpression of Trib3 alone in ESCs was able to decrease HPC production, though not as great as seen with miR-24 knockdown. These results demonstrate an essential role for miR-24 in the hematopoietic differentiation of ESCs. Although many miRNAs have been implicated in regulation of hematopoiesis, this is the first miRNA observed to be required for the specification of mammalian blood progenitors from early mesoderm.

Original languageEnglish (US)
Article numbere1004959
JournalPLoS Genetics
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2015

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embryonic stem cells
Mesoderm
stem
Hemangioblasts
Embryonic Stem Cells
hematopoiesis
MicroRNAs
blood
mice
microRNA
endothelial cells
Hematopoiesis
Endothelial Cells
Embryoid Bodies
blood cells
B-lymphocytes
defect
phenotype
muscle
Cardiac Myocytes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

MiR-24 Is Required for Hematopoietic Differentiation of Mouse Embryonic Stem Cells. / Roy, Lynn; Bikorimana, Emmanuel; Lapid, Danica; Choi, Hyewon; Nguyen, Tan; Dahl, Richard.

In: PLoS Genetics, Vol. 11, No. 1, e1004959, 01.01.2015.

Research output: Contribution to journalArticle

Roy, Lynn ; Bikorimana, Emmanuel ; Lapid, Danica ; Choi, Hyewon ; Nguyen, Tan ; Dahl, Richard. / MiR-24 Is Required for Hematopoietic Differentiation of Mouse Embryonic Stem Cells. In: PLoS Genetics. 2015 ; Vol. 11, No. 1.
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