Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs

Illich DJ, Zhang M, Ursu A, Osorno R, Kim KP, Yoon J, Arauzo-Bravo MJ, Wu G, Esch D, Sabour D, Colby D, Grassme KS, Chen J, Greber B, Hoeing S, Herzog W, Ziegler S, Chambers I, Gao S, Waldmann H, Schoeler HR (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 15

Pages Range: 787-800

Journal Issue: 4

DOI: 10.1016/j.celrep.2016.03.073

Abstract

It has previously been reported that mouse epiblast stem cell (EpiSC) lines comprise heterogeneous cell populations that are functionally equivalent to cells of either early- or late-stage postimplantation development. So far, the establishment of the embryonic stem cell (ESC) pluripotency gene regulatory network through the widely known chemical inhibition of MEK and GSK3beta has been impractical in late-stage EpiSCs. Here, we show that chemical inhibition of casein kinase 1alpha (CK1alpha) induces the conversion of recalcitrant late-stage EpiSCs into ESC pluripotency. CK1alpha inhibition directly results in the simultaneous activation of the WNT signaling pathway, together with inhibition of the TGFbeta/SMAD2 signaling pathway, mediating the rewiring of the gene regulatory network in favor of an ESC-like state. Our findings uncover a molecular mechanism that links CK1alpha to ESC pluripotency through the direct modulation of WNT and TGFbeta signaling.

Authors with CRIS profile

Wiebke Herzog

Involved external institutions

Max-Planck-Institut für molekulare Biomedizin / Max Planck Institute for Molecular Biomedicine DE Germany (DE) Tongji University / 同济大学 CN China (CN) Max-Planck-Institut für molekulare Physiologie / Max Planck Institute of Molecular Physiology DE Germany (DE) University of Edinburgh GB United Kingdom (GB) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE)

How to cite

APA:

Illich, D.J., Zhang, M., Ursu, A., Osorno, R., Kim, K.-P., Yoon, J.,... Schoeler, H.R. (2016). Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs. Cell Reports, 15(4), 787-800. https://doi.org/10.1016/j.celrep.2016.03.073

MLA:

Illich, Damir Jacob, et al. "Distinct Signaling Requirements for the Establishment of ESC Pluripotency in Late-Stage EpiSCs." Cell Reports 15.4 (2016): 787-800.

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