Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis
© 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) incl...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022
|
| Online Access: | https://hdl.handle.net/1721.1/135061.2 |
| _version_ | 1811088155402567680 |
|---|---|
| author | Rennerfeldt, Deena A Raminhos, Joana S. Leff, Samantha M Manning, Pristinavae Van Vliet, Krystyn J |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Rennerfeldt, Deena A Raminhos, Joana S. Leff, Samantha M Manning, Pristinavae Van Vliet, Krystyn J |
| author_sort | Rennerfeldt, Deena A |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T13:57:09Z |
| format | Article |
| id | mit-1721.1/135061.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:57:09Z |
| publishDate | 2022 |
| publisher | Public Library of Science (PLoS) |
| record_format | dspace |
| spelling | mit-1721.1/135061.22022-07-06T19:28:20Z Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis Rennerfeldt, Deena A Raminhos, Joana S. Leff, Samantha M Manning, Pristinavae Van Vliet, Krystyn J Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering © 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. 2022-07-06T19:28:18Z 2021-10-27T20:10:33Z 2022-07-06T19:28:18Z 2019 2019-09-24T17:59:46Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135061.2 en 10.1371/journal.pone.0213452 PLoS ONE Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/octet-stream Public Library of Science (PLoS) PLoS |
| spellingShingle | Rennerfeldt, Deena A Raminhos, Joana S. Leff, Samantha M Manning, Pristinavae Van Vliet, Krystyn J Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title | Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title_full | Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title_fullStr | Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title_full_unstemmed | Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title_short | Emergent heterogeneity in putative mesenchymal stem cell colonies: Single-cell time lapsed analysis |
| title_sort | emergent heterogeneity in putative mesenchymal stem cell colonies single cell time lapsed analysis |
| url | https://hdl.handle.net/1721.1/135061.2 |
| work_keys_str_mv | AT rennerfeldtdeenaa emergentheterogeneityinputativemesenchymalstemcellcoloniessinglecelltimelapsedanalysis AT raminhosjoanas emergentheterogeneityinputativemesenchymalstemcellcoloniessinglecelltimelapsedanalysis AT leffsamantham emergentheterogeneityinputativemesenchymalstemcellcoloniessinglecelltimelapsedanalysis AT manningpristinavae emergentheterogeneityinputativemesenchymalstemcellcoloniessinglecelltimelapsedanalysis AT vanvlietkrystynj emergentheterogeneityinputativemesenchymalstemcellcoloniessinglecelltimelapsedanalysis |