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Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.

Nature | Feb 4, 2010

When embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In the absence of DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to silence self-renewal. Here we show that the introduction of let-7 miRNAs-a family of miRNAs highly expressed in somatic cells-can suppress self-renewal in Dgcr8(-/-) but not wild-type ESCs. Introduction of ESC cell cycle regulating (ESCC) miRNAs into the Dgcr8(-/-) ESCs blocks the capacity of let-7 to suppress self-renewal. Profiling and bioinformatic analyses show that let-7 inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes. Furthermore, inhibition of the let-7 family promotes de-differentiation of somatic cells to induced pluripotent stem cells. Together, these findings show how the ESCC and let-7 miRNAs act through common pathways to alternatively stabilize the self-renewing versus differentiated cell fates.

Pubmed ID: 20054295 RIS Download

Mesh terms: 3' Untranslated Regions | Animals | Cell Dedifferentiation | Cell Lineage | Cell Proliferation | Cellular Reprogramming | Computational Biology | DNA-Binding Proteins | Embryonic Stem Cells | Gene Silencing | Genes, myc | Induced Pluripotent Stem Cells | Mice | MicroRNAs | Open Reading Frames | Proteins | RNA-Binding Proteins | Transcription Factors | Transcription, Genetic

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Associated grants

  • Agency: , Id: K08 NS048118-03
  • Agency: , Id: K08 NS048118-04
  • Agency: , Id: K08 NS048118-05
  • Agency: , Id: R01 NS057221-03
  • Agency: NINDS NIH HHS, Id: K08 NS48118
  • Agency: , Id: R01 NS057221-02
  • Agency: , Id: K08 NS048118-02
  • Agency: NINDS NIH HHS, Id: K08 NS048118
  • Agency: , Id: R01 NS057221-01A1
  • Agency: NINDS NIH HHS, Id: R01 NS057221

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