Strano, A;
Tuck, E;
Stubbs, VE;
Livesey, FJ;
(2020)
Variable Outcomes in Neural Differentiation of Human PSCs Arise from Intrinsic Differences in Developmental Signaling Pathways.
Cell Reports
, 31
(10)
, Article 107732. 10.1016/j.celrep.2020.107732.
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Abstract
Directed differentiation of human pluripotent stem cells varies in specificity and efficiency. Stochastic, genetic, intracellular, and environmental factors affect maintenance of pluripotency and differentiation into early embryonic lineages. However, factors affecting variation in in vitro differentiation to defined cell types are not well understood. To address this, we focused on a well-established differentiation process to cerebral cortex neural progenitor cells and their neuronal progeny from human pluripotent stem cells. Analysis of 162 differentiation outcomes of 61 stem cell lines derived from 37 individuals showed that most variation occurs along gene expression axes reflecting dorsoventral and rostrocaudal spatial expression during in vivo brain development. Line-independent and line-dependent variations occur, with the latter driven largely by differences in endogenous Wnt signaling activity. Tuning Wnt signaling during a specific phase early in the differentiation process reduces variability, demonstrating that cell-line/genome-specific differentiation outcome biases can be corrected by controlling extracellular signaling.
| Type: | Article |
|---|---|
| Title: | Variable Outcomes in Neural Differentiation of Human PSCs Arise from Intrinsic Differences in Developmental Signaling Pathways. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2020.107732 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2020.107732 |
| Language: | English |
| Additional information: | © 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Hh signalling, Wnt signalling, cortical differentiation, dual SMAD inhibition, hPSC variation, human puripotent stem cell, neural induction, patterning of the cortex, regional identity specification, transcriptional profiling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10101478 |
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