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Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations

Park, Jong H. and Tsou, Tiffany and Rivaud, Paul and Thomson, Matt and Chen, Sisi (2019) Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations. . (Unpublished)

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Stem cell populations within developing embryos are diverse, composed of many different subpopulations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Tsou, Tiffany0000-0002-5651-2879
Rivaud, Paul0000-0001-8637-3331
Chen, Sisi0000-0001-9448-9713
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Dec. 31, 2019. Allan Pool-Hermann, Carlos Lois, David Schaffer, Elliott Robinson, Eric Chow, Chris McGinnis, Jase Gehring, Sandy Nandagopal, Michael Elowitz, Elisha Mackay, Thomson Lab, Beckman Institute Single-cell Profiling and Engineering Center (SPEC).
Record Number:CaltechAUTHORS:20200102-083334191
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Official Citation:Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations. Jong H. Park, Tiffany Tsou, Paul Rivaud, Matt Thomson, Sisi Chen. bioRxiv 2019.12.30.890087; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100442
Deposited By: Tony Diaz
Deposited On:02 Jan 2020 19:46
Last Modified:18 Nov 2020 20:12

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