Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation.

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Stirparo, Giuliano G 

Human naïve pluripotent stem cells (PSCs) share features with the pre-implantation epiblast. They therefore provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens Here, we confirm that naïve PSCs do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole-transcriptome profiling during this formative transition highlights dynamic changes in gene expression, which affect many cellular properties including metabolism and epithelial features. Notably, naïve pluripotency factors are exchanged for postimplantation factors, but competent cells remain devoid of lineage-specific transcription. The gradual pace of transition for human naïve PSCs is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human naïve cells tracks the progression of the epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus, the formative transition of naïve PSCs in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis.

Competence, Differentiation, Epiblast, Human embryo, Lineage specification, Pluripotent stem cell, Animals, Blastocyst, Cell Differentiation, Cell Lineage, Embryo, Mammalian, Embryonic Stem Cells, Gene Expression Regulation, Developmental, Germ Layers, Humans, Mice, Pluripotent Stem Cells, Signal Transduction
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The Company of Biologists
Medical Research Council (G1001028)
Medical Research Council (MR/P00072X/1)
Medical Research Council (MR/L012537/1)
This research was funded by the Medical Research Council of the United Kingdom (G1001028 and MR/P00072X/1), the European Commission Framework 7 (HEALTH-F4-2013-602423, PluriMes) and the UK Regenerative Medicine Platform (MR/L012537/1). The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and the Medical Research Council. AS is a Medical Research Council Professor.