The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells

Julia Ye1,2,3, Ryan M Boileau1,2,3, Ronald J Parchem4

  • 1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, CA 94143, United States.

PubMed

Insights

The miR-290 and miR-302 microRNA clusters are essential for induced pluripotency. Their combined absence blocks reprogramming, highlighting their interchangeable roles in generating induced pluripotent stem cells (iPSCs).

Area of Science:

  • Stem cell biology
  • Molecular and cellular biology

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression.
  • The miR-290 and miR-302 clusters are highly expressed in embryonic stem cells (ESCs).
  • These miRNA clusters enhance the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs).

Purpose of the Study:

  • To investigate the specific roles of the miR-290 and miR-302 clusters in the reprogramming process.
  • To determine if these clusters are essential or interchangeable for generating induced pluripotent stem cells (iPSCs).

Main Methods:

  • Genetic knockouts of miR-290 and miR-302 clusters in mouse fibroblasts.
  • Reprogramming using retroviral delivery of Oct4, Sox2, and Klf4.
  • Analysis of reprogramming efficiency, cell proliferation, pluripotency factor silencing, and transcriptome.

Main Results:

  • Individual knockout of miR-290 or miR-302 clusters did not impair reprogramming efficiency.
  • Combined knockout of both clusters completely blocked iPSC formation.
  • Double knockout clones exhibited reduced proliferation, incomplete silencing of reprogramming factors, and distinct transcriptomes.

Conclusions:

  • The miR-290 and miR-302 clusters are essential for reprogramming somatic cells to induced pluripotency.
  • These two clusters are functionally interchangeable, with either one sufficient to support reprogramming when the other is absent.

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