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MicroRNA programs in normal and aberrant stem and progenitor cells.

Emerging evidence suggests that microRNAs (miRNAs), an abundant class of ∼22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.

Pubmed ID: 21451113

Authors

  • Arnold CP
  • Tan R
  • Zhou B
  • Yue SB
  • Schaffert S
  • Biggs JR
  • Doyonnas R
  • Lo MC
  • Perry JM
  • Renault VM
  • Sacco A
  • Somervaille T
  • Viatour P
  • Brunet A
  • Cleary ML
  • Li L
  • Sage J
  • Zhang DE
  • Blau HM
  • Chen C
  • Chen CZ

Journal

Genome research

Publication Data

May 3, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: DP1 CA174421
  • Agency: NIH HHS, Id: DP1 OD006435
  • Agency: NIH HHS, Id: DP1 OD006435-02
  • Agency: NIH HHS, Id: DP1 OD006435-03
  • Agency: NIA NIH HHS, Id: R01 AG020961
  • Agency: NIAID NIH HHS, Id: R01 AI073724
  • Agency: NIAID NIH HHS, Id: R01 AI073724-03
  • Agency: NCI NIH HHS, Id: R01 CA104509
  • Agency: NHLBI NIH HHS, Id: R01 HL081612
  • Agency: NHLBI NIH HHS, Id: R01 HL081612-04W1
  • Agency: NHLBI NIH HHS, Id: R01 HL081612-05
  • Agency: NIAID NIH HHS, Id: T32 AI007290
  • Agency: NHLBI NIH HHS, Id: U01 HL100397

Mesh Terms

  • Animals
  • Cell Differentiation
  • Embryonic Stem Cells
  • Gene Expression Regulation
  • Hematopoietic Stem Cells
  • Humans
  • Mice
  • MicroRNAs
  • Mutation
  • Myoblasts
  • Neural Stem Cells
  • Organ Specificity
  • Stem Cells