MicroRNAs organize intrinsic variation into stem cell states
© 2020 National Academy of Sciences. All rights reserved. Pluripotent embryonic stem cells (ESCs) contain the potential to form a diverse array of cells with distinct gene expression states, namely the cells of the adult vertebrate. Classically, diversity has been attributed to cells sensing their p...
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2021
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| Online Access: | https://hdl.handle.net/1721.1/136242 |
| _version_ | 1826205036735102976 |
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| author | Chakraborty, Meenakshi Hu, Sofia Visness, Erica Del Giudice, Marco De Martino, Andrea Bosia, Carla Sharp, Phillip A Garg, Salil |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Chakraborty, Meenakshi Hu, Sofia Visness, Erica Del Giudice, Marco De Martino, Andrea Bosia, Carla Sharp, Phillip A Garg, Salil |
| author_sort | Chakraborty, Meenakshi |
| collection | MIT |
| description | © 2020 National Academy of Sciences. All rights reserved. Pluripotent embryonic stem cells (ESCs) contain the potential to form a diverse array of cells with distinct gene expression states, namely the cells of the adult vertebrate. Classically, diversity has been attributed to cells sensing their position with respect to external morphogen gradients. However, an alternative is that diversity arises in part from cooption of fluctuations in the gene regulatory network. Here we find ESCs exhibit intrinsic heterogeneity in the absence of external gradients by forming interconverting cell states. States vary in developmental gene expression programs and display distinct activity of microRNAs (miRNAs). Notably, miRNAs act on neighborhoods of pluripotency genes to increase variation of target genes and cell states. Loss of miRNAs that vary across states reduces target variation and delays state transitions, suggesting variable miRNAs organize and propagate variation to promote state transitions. Together these findings provide insight into how a gene regulatory network can coopt variation intrinsic to cell systems to form robust gene expression states. Interactions between intrinsic heterogeneity and environmental signals may help achieve developmental outcomes. |
| first_indexed | 2024-09-23T13:06:03Z |
| format | Article |
| id | mit-1721.1/136242 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:06:03Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1362422023-09-14T19:29:38Z MicroRNAs organize intrinsic variation into stem cell states Chakraborty, Meenakshi Hu, Sofia Visness, Erica Del Giudice, Marco De Martino, Andrea Bosia, Carla Sharp, Phillip A Garg, Salil Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology Harvard University--MIT Division of Health Sciences and Technology © 2020 National Academy of Sciences. All rights reserved. Pluripotent embryonic stem cells (ESCs) contain the potential to form a diverse array of cells with distinct gene expression states, namely the cells of the adult vertebrate. Classically, diversity has been attributed to cells sensing their position with respect to external morphogen gradients. However, an alternative is that diversity arises in part from cooption of fluctuations in the gene regulatory network. Here we find ESCs exhibit intrinsic heterogeneity in the absence of external gradients by forming interconverting cell states. States vary in developmental gene expression programs and display distinct activity of microRNAs (miRNAs). Notably, miRNAs act on neighborhoods of pluripotency genes to increase variation of target genes and cell states. Loss of miRNAs that vary across states reduces target variation and delays state transitions, suggesting variable miRNAs organize and propagate variation to promote state transitions. Together these findings provide insight into how a gene regulatory network can coopt variation intrinsic to cell systems to form robust gene expression states. Interactions between intrinsic heterogeneity and environmental signals may help achieve developmental outcomes. 2021-10-27T20:34:27Z 2021-10-27T20:34:27Z 2020 2021-08-02T17:55:56Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136242 en 10.1073/PNAS.1920695117 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Chakraborty, Meenakshi Hu, Sofia Visness, Erica Del Giudice, Marco De Martino, Andrea Bosia, Carla Sharp, Phillip A Garg, Salil MicroRNAs organize intrinsic variation into stem cell states |
| title | MicroRNAs organize intrinsic variation into stem cell states |
| title_full | MicroRNAs organize intrinsic variation into stem cell states |
| title_fullStr | MicroRNAs organize intrinsic variation into stem cell states |
| title_full_unstemmed | MicroRNAs organize intrinsic variation into stem cell states |
| title_short | MicroRNAs organize intrinsic variation into stem cell states |
| title_sort | micrornas organize intrinsic variation into stem cell states |
| url | https://hdl.handle.net/1721.1/136242 |
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