Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation.
Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self-renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation-specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine.
Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, Belvaux, Luxembourg.
Vladimir
V
Espinosa Angarica
Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, Belvaux, Luxembourg.
Antonio
A
Del Sol
D000818:Animals; D002454:Cell Differentiation; D053263:Gene Regulatory Networks; D006801:Humans; D039904:Pluripotent Stem Cells / Q000502:physiology*; D044968:Regenerative Medicine / Q000379:methods*; D059010:Single-Cell Analysis
gene expression heterogeneity; gene regulatory network; regenerative medicine; stem cell differentiation