Deconstructing the pluripotency gene regulatory network

Abstract

Pluripotent stem cells can be isolated from embryos or derived by reprogramming. Pluripotency is stabilized by an interconnected network of pluripotency genes that cooperatively regulate gene expression. Here we describe the molecular principles of pluripotency gene function and highlight post-transcriptional controls, particularly those induced by RNA-binding proteins and alternative splicing, as an important regulatory layer of pluripotency. We also discuss heterogeneity in pluripotency regulation, alternative pluripotency states and future directions of pluripotent stem cell research.

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Fig. 1: Core transcription factors and regulatory crosstalks of PGRN.
Fig. 2: Cooperative binding of the core pluripotency transcription factors.
Fig. 3: The RNA-binding protein LIN28 plays key roles in pluripotency regulation.

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Acknowledgements

We apologize to the colleagues whose works are not covered due to space constraint. We would like to thank May Schwarz, Peter Schwarz, Chunmei Xia and Xingxing Zhang for generous administrative help during the preparation of the manuscript. We would like to thank the anonymous reviewers whose input has resulted in an improved manuscript. Work in the laboratory of M.L. was supported by King Abdullah University of Science and Technology (KAUST). Work in the laboratory of J.C.I.B. was supported by the G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002), the Moxie Foundation, NIH (5 DP1 DK113616 and R21AG055938), Progeria Research Foundation, Fundacion Dr. Pedro Guillen and the Universidad Católica San Antonio de Murcia (UCAM).

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Li, M., Izpisua Belmonte, J.C. Deconstructing the pluripotency gene regulatory network. Nat Cell Biol 20, 382–392 (2018). https://doi.org/10.1038/s41556-018-0067-6

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