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Oct4 Contributes to Mesodermal Differentiation by Sustaining the Proliferative Capacity of Early Mesodermal

Anastasiia V Lukacheva1, Anna S Zinovyeva1, Andrey A Kuzmin1

  • 1Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia.

International Journal of Molecular Sciences
|January 10, 2026
PubMed
Summary

Oct4 (Octamer-binding transcription factor 4) is crucial for maintaining cell proliferation during mesodermal differentiation. Its loss impairs mesoderm development and reduces cardiomyocyte formation.

Keywords:
Oct4cell proliferationembryoid bodieslineage specificationmesodermal differentiationpluripotency

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Oct4 is a key regulator of pluripotency.
  • Emerging evidence suggests Oct4 also plays a role in lineage specification during the exit from pluripotency.
  • Oct4 expression is observed in early mesodermal progenitors, but its function in this context is unclear.

Purpose of the Study:

  • To investigate the precise function of Oct4 in early mesodermal progenitors.
  • To understand the consequences of Oct4 loss during the exit from the pluripotent state.
  • To elucidate Oct4's role in mesodermal lineage specification using embryoid bodies (EBs).

Main Methods:

  • Utilized embryoid bodies (EBs) as a model for spontaneous differentiation in vitro.
  • Performed reporter assays to analyze gene expression patterns.
  • Generated conditional knockout of the Oct4 gene to study loss-of-function effects.

Main Results:

  • Observed transient co-expression of Oct4 and Brachyury in EBs, confirming Oct4's role in early mesodermal progenitors.
  • Oct4 knockout led to reduced EB size and cell cycle arrest in G0/G1 phase, highlighting Oct4's requirement for proliferation.
  • Despite proliferation defects, cells could still initiate multilineage differentiation, but with altered marker expression (reduced Brachyury, elevated FoxA2 and Sox17).
  • Diminished formation of beating cardiomyocyte-like structures was observed upon Oct4 loss.

Conclusions:

  • Oct4 plays a critical role in mesodermal differentiation by maintaining the proliferative capacity of early mesodermal progenitors.
  • Oct4 influences the balance of mesodermal and endodermal lineage specification.
  • Oct4 is essential for proper cardiomyocyte development from early mesodermal progenitors.