Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate
Tischler J, Gruhn WH, Reid J, Allgeyer E, Buettner F, Marr C, Theis F, Simons BD, Wernisch L, Surani MA (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 38
Article Number: e99518
Journal Issue: 1
Abstract
An intricate link is becoming apparent between metabolism and cellular identities. Here, we explore the basis for such a link in an in vitro model for early mouse embryonic development: from naïve pluripotency to the specification of primordial germ cells (PGCs). Using single-cell RNA-seq with statistical modelling and modulation of energy metabolism, we demonstrate a functional role for oxidative mitochondrial metabolism in naïve pluripotency. We link mitochondrial tricarboxylic acid cycle activity to IDH2-mediated production of alpha-ketoglutarate and through it, the activity of key epigenetic regulators. Accordingly, this metabolite has a role in the maintenance of naïve pluripotency as well as in PGC differentiation, likely through preserving a particular histone methylation status underlying the transient state of developmental competence for the PGC fate. We reveal a link between energy metabolism and epigenetic control of cell state transitions during a developmental trajectory towards germ cell specification, and establish a paradigm for stabilizing fleeting cellular states through metabolic modulation.
Involved external institutions
University of Cambridge
United Kingdom (GB)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
United Kingdom (GB)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
How to cite
APA:
Tischler, J., Gruhn, W.H., Reid, J., Allgeyer, E., Buettner, F., Marr, C.,... Surani, M.A. (2019). Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate. EMBO Journal, 38(1). https://dx.doi.org/10.15252/embj.201899518
MLA:
Tischler, Julia, et al. "Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate." EMBO Journal 38.1 (2019).
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