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

Lukacheva, Anastasiia V.; Zinovyeva, Anna S.; Kuzmin, Andrey A.; Gordeev, Mikhail N.; Vasilin, Vladislav V.; Kriger, Daria V.; Aksenov, Nikolay D.; Tomilin, Alexey N.; Bakhmet, Evgeny I.

doi:10.3390/ijms27010054

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

by

Anastasiia V. Lukacheva

,

Anna S. Zinovyeva

,

Andrey A. Kuzmin

,

Mikhail N. Gordeev

^†,

Vladislav V. Vasilin

,

Daria V. Kriger

,

Nikolay D. Aksenov

,

Alexey N. Tomilin

and

Evgeny I. Bakhmet

^*

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

^*

Author to whom correspondence should be addressed.

^†

Current address: Institute of Evolution, University of Haifa, Haifa 3498838, Israel.

Int. J. Mol. Sci. 2026, 27(1), 54; https://doi.org/10.3390/ijms27010054 (registering DOI)

Submission received: 21 November 2025 / Revised: 12 December 2025 / Accepted: 18 December 2025 / Published: 20 December 2025

(This article belongs to the Special Issue Fundamental and Practical Perspectives in Regenerative Medicine: Proceedings of the VI National Congress of Regenerative Medicine (2024))

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Abstract

Oct4 is well established as a core regulator of pluripotency, yet emerging evidence points to an additional role in lineage specification during the exit from the pluripotent state. Although Oct4 expression has been observed in early mesodermal progenitors, its precise function in this developmental context remains unclear. To investigate this, we employed embryoid bodies (EBs) as a model of spontaneous differentiation that recapitulates key aspects of early embryonic development in vitro. In accordance with previous studies, reporter assay revealed a distinct temporal pattern characterized by the strong, transient co-expression of Oct4 and the early mesoderm-specifying marker gene Brachyury within a narrow developmental window, consistent with the Oct4 role in early mesodermal progenitors. We further examined the consequences of the Oct4 loss at early stages of this differentiation. Conditional knockout of the Oct4 gene resulted in a significant reduction in EB size and accumulation of cells in the G0/G1 phase, indicating a critical requirement for Oct4 in maintaining cell proliferation. Despite this defect, cells retained the ability to initiate multilineage differentiation, albeit with reduced expression of Brachyury and elevated expression of endodermal markers FoxA2 and Sox17. Interestingly, the formation of beating cardiomyocyte-like structures was also diminished following Oct4 loss and could not be rescued by simply increasing cell numbers. Taken together, these findings highlight an important Oct4 function in mesodermal differentiation, mediated through the maintenance of proliferative capacity of early mesodermal progenitors.

Keywords: Oct4; pluripotency; embryoid bodies; mesodermal differentiation; cell proliferation; lineage specification

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MDPI and ACS Style

Lukacheva, A.V.; Zinovyeva, A.S.; Kuzmin, A.A.; Gordeev, M.N.; Vasilin, V.V.; Kriger, D.V.; Aksenov, N.D.; Tomilin, A.N.; Bakhmet, E.I. Oct4 Contributes to Mesodermal Differentiation by Sustaining the Proliferative Capacity of Early Mesodermal Progenitors. Int. J. Mol. Sci. 2026, 27, 54. https://doi.org/10.3390/ijms27010054

AMA Style

Lukacheva AV, Zinovyeva AS, Kuzmin AA, Gordeev MN, Vasilin VV, Kriger DV, Aksenov ND, Tomilin AN, Bakhmet EI. Oct4 Contributes to Mesodermal Differentiation by Sustaining the Proliferative Capacity of Early Mesodermal Progenitors. International Journal of Molecular Sciences. 2026; 27(1):54. https://doi.org/10.3390/ijms27010054

Chicago/Turabian Style

Lukacheva, Anastasiia V., Anna S. Zinovyeva, Andrey A. Kuzmin, Mikhail N. Gordeev, Vladislav V. Vasilin, Daria V. Kriger, Nikolay D. Aksenov, Alexey N. Tomilin, and Evgeny I. Bakhmet. 2026. "Oct4 Contributes to Mesodermal Differentiation by Sustaining the Proliferative Capacity of Early Mesodermal Progenitors" International Journal of Molecular Sciences 27, no. 1: 54. https://doi.org/10.3390/ijms27010054

APA Style

Lukacheva, A. V., Zinovyeva, A. S., Kuzmin, A. A., Gordeev, M. N., Vasilin, V. V., Kriger, D. V., Aksenov, N. D., Tomilin, A. N., & Bakhmet, E. I. (2026). Oct4 Contributes to Mesodermal Differentiation by Sustaining the Proliferative Capacity of Early Mesodermal Progenitors. International Journal of Molecular Sciences, 27(1), 54. https://doi.org/10.3390/ijms27010054

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

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