Signalling pathway crosstalk stimulated by L-proline drives mouse embryonic stem cells to primitive-ectoderm-like cells.

Autor:	Glover HJ; School of Medical Sciences, University of Sydney, Sydney 2006, Australia.; Naomi Berrie Diabetes Center, Columbia Stem Cell Initiative, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA., Holliday H; School of Medical Sciences, University of Sydney, Sydney 2006, Australia., Shparberg RA; School of Medical Sciences, University of Sydney, Sydney 2006, Australia., Winkler D; Department of Biochemistry and Chemistry, Latrobe Institute for Molecular Science, Latrobe University, Bundoora 3083, Australia.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia.; Advanced Materials and Healthcare Technologies, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK., Day M; School of Medical Sciences, University of Sydney, Sydney 2006, Australia., Morris MB; School of Medical Sciences, University of Sydney, Sydney 2006, Australia.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2023 Oct 15; Vol. 150 (20). Date of Electronic Publication: 2023 Oct 26.
DOI:	10.1242/dev.201704
Abstrakt:	The amino acid L-proline exhibits growth factor-like properties during development - from improving blastocyst development to driving neurogenesis in vitro. Addition of 400 μM L-proline to self-renewal medium drives naïve mouse embryonic stem cells (ESCs) to early primitive ectoderm-like (EPL) cells - a transcriptionally distinct primed or partially primed pluripotent state. EPL cells retain expression of pluripotency genes, upregulate primitive ectoderm markers, undergo a morphological change and have increased cell number. These changes are facilitated by a complex signalling network hinging on the Mapk, Fgfr, Pi3k and mTor pathways. Here, we use a factorial experimental design coupled with statistical modelling to understand which signalling pathways are involved in the transition between ESCs and EPL cells, and how they underpin changes in morphology, cell number, apoptosis, proliferation and gene expression. This approach reveals pathways which work antagonistically or synergistically. Most properties were affected by more than one inhibitor, and each inhibitor blocked specific aspects of the naïve-to-primed transition. These mechanisms underpin progression of stem cells across the in vitro pluripotency continuum and serve as a model for pre-, peri- and post-implantation embryogenesis. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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