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Updated: Mar 8, 2026

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
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Noncanonical function of DGCR8 controls mESC exit from pluripotency

Daniel Cirera-Salinas1, Jian Yu1,2, Maxime Bodak1,2

  • 1Department of Biology, Institute of Molecular Health Sciences, RNAi and Genome Integrity, Swiss Federal Institute of Technology Zurich, Zurich 8093, Switzerland.

The Journal of Cell Biology
|January 20, 2017
PubMed

Insights

DGCR8 is crucial for mouse stem cell differentiation, controlling pluripotency exit. Beyond microRNA processing, DGCR8 regulates Tcf7l1 splicing, a key step for stem cell differentiation.

Area of Science:

  • Stem cell biology
  • Molecular genetics
  • RNA biology

Background:

  • Mouse embryonic stem cells (mESCs) lacking DGCR8 exhibit differentiation defects.
  • The precise mechanisms behind these pluripotency commitment failures are not fully understood.

Purpose of the Study:

  • To elucidate the role of DGCR8 in mESC differentiation and pluripotency exit.
  • To differentiate between canonical and noncanonical functions of DGCR8.

Main Methods:

  • Generation and analysis of DGCR8-deficient mESCs.
  • Complementation with a phosphomutant DGCR8.
  • Integration of omics data and RNA immunoprecipitation (RIP).

Main Results:

  • DGCR8 is essential for exiting the pluripotent state in mESCs.
  • A phosphomutant DGCR8 restored microRNA levels but not pluripotency exit.
  • DGCR8 directly interacts with Tcf7l1 mRNA, a pluripotency factor.
  • DGCR8 facilitates Tcf7l1 splicing, which is critical for mESC differentiation.

Conclusions:

  • DGCR8 plays a noncanonical role in modulating alternative splicing of Tcf7l1 mRNA.
  • This splicing function is independent of its established role in microRNA biogenesis.
  • DGCR8 is vital for regulating stem cell differentiation through alternative splicing.

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