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Global splicing pattern reversion during somatic cell reprogramming.

Sho Ohta1, Eisuke Nishida, Shinya Yamanaka

  • 1Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

Cell Reports
|October 22, 2013
PubMed
Summary
This summary is machine-generated.

Somatic cell splicing profiles revert to pluripotent ones during cell reprogramming. Key RNA-binding proteins like U2af1 and Srsf3 are crucial for this splicing alteration and reprogramming process.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Stem Cell Biology

Background:

  • Alternative splicing generates diverse transcripts from a single gene.
  • Cell-type-specific splicing is vital for cellular properties and functions.
  • Somatic cells can dedifferentiate into pluripotent cells via transcription factor expression.

Purpose of the Study:

  • To investigate whether somatic cell splicing patterns are reorganized during cellular reprogramming.
  • To identify RNA-binding proteins involved in splicing regulation during induced pluripotent stem cell (iPSC) generation.

Main Methods:

  • Deep sequencing was employed to analyze splicing profiles.
  • High-throughput absolute quantitative reverse transcription PCR (qRT-PCR) was utilized.
  • A small interfering RNA (siRNA) screen was performed to identify regulatory RNA-binding proteins.

Main Results:

  • Somatic splicing profiles were observed to revert to pluripotent profiles during reprogramming.
  • Pluripotent stem cell splicing patterns share similarities with those found in testes.
  • Specific RNA-binding proteins, including U2af1 and Srsf3, were identified as regulators of splicing events in iPSCs and play a role in reprogramming.

Conclusions:

  • The study demonstrates a significant alteration in splicing patterns during somatic cell reprogramming.
  • This drastic splicing change is an integral component of the molecular network governing the reprogramming process.
  • Identified RNA-binding proteins are critical for mediating these splicing changes and facilitating reprogramming.