• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.

The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.

Pubmed ID: 21490602

Authors

  • Subramanyam D
  • Lamouille S
  • Judson RL
  • Liu JY
  • Bucay N
  • Derynck R
  • Blelloch R

Journal

Nature biotechnology

Publication Data

May 9, 2011

Associated Grants

  • Agency: NINDS NIH HHS, Id: K08 NS048118
  • Agency: NINDS NIH HHS, Id: K08 NS048118-01A1
  • 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 NS048118-06
  • 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
  • Agency: NINDS NIH HHS, Id: R01 NS057221-04
  • Agency: NINDS NIH HHS, Id: R01 NS057221-04S1
  • Agency: NCI NIH HHS, Id: R01-CA136690

Mesh Terms

  • Blotting, Western
  • Cell Differentiation
  • Cell Line
  • Embryonic Stem Cells
  • Epigenomics
  • Epithelial-Mesenchymal Transition
  • Fibroblasts
  • Gene Expression Regulation, Developmental
  • Humans
  • Induced Pluripotent Stem Cells
  • Keratinocytes
  • MicroRNAs
  • Polymerase Chain Reaction
  • Transforming Growth Factor beta