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

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

Authors

  • Melton C
  • Judson RL
  • Blelloch R

Journal

Nature

Publication Data

February 4, 2010

Associated Grants

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

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