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Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis
Name
journal.pone.0213452.pdf
Description
Published version
Size
4.47 MB
Format
Adobe PDF
Checksum (MD5)
0821983ba6010a2023ffae1b30922d2c
Author(s)
Rennerfeldt, Deena A
Raminhos, Joana S
Leff, Samantha M
Manning, Pristinavae
Van Vliet, Krystyn J
Date Issued
2019
Journal
PLoS ONE
Publisher
Public Library of Science (PLoS)
Version
Final published version
Abstract
© 2019 Rennerfeldt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Bone marrow stromal cells (BMSCs) include a subset of stem cells that are considered promising for developmental studies and therapeutic applications. While it is appreciated generally that BMSC populations can exhibit morphological and functional heterogeneity upon in vitro culture expansion, the potential for heterogeneity within a single colony forming unit–generated ostensibly from a single mother cell–is less explored but is critical to design of both fundamental studies and cell therapy production. Here we observed BMSC colony formation in real time via time lapsed optical imaging and analysis, to quantify whether and how heterogeneity emerged over multiple cell divisions spanning the duration of a typical colony formation unit assay. These analyses demonstrate that such colonies are neither homogeneous subpopulations of stem cells nor necessarily derived from single originating cells. While the mechanisms for and causes of this intracolony heterogeneity are not understood fully, we further demonstrate that extensive cell-cell contacts do not correlate with senescence, but that media exchange was concurrent with diversification in even the most uniform single-cell-derived colonies. These direct quantitative observations and visualizations of colony formation provide new insights that are motivated by significant implications for both basic research and stem cell-based therapies.
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1371/journal.pone.0213452
