The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice
Open accessAbstract
Adult stem cells occur in niches that balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, stem cells outside their niche often display fate flexibility. Here we show that super-enhancers underlie the identity, lineage commitment and plasticity of adult stem cells in vivo. Using hair follicle as a model, we map the global chromatin domains of hair follicle stem cells and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicentres’) of transcription factor binding sites undergo remodelling upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicentres, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, hair follicle stem cells dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicentres, enabling their genes to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of hair follicle stem cell super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense transcription-factor-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status but also stemness, plasticity in transitional states and differentiation.
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Cites
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Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
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Inflammatory memory sensitizes skin epithelial stem cells to tissue damage
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Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis
Matsumura, H., Mohri, Y., Binh, N. T., Morinaga, H., Fukuda, M., Ito, M., Kurata, S., Hoeijmakers, J., & Nishimura, E. K. (2016) · Science · doi:10.1126/science.aad4395 · Cited by 416
Metadata
- Authors
- Adam, R. C., Yang, H., Rockowitz, S., Larsen, S. B., Nikolova, M., Oristian, D. S., Polak, L., Kadaja, M., Asare, A., Zheng, D., & Fuchs, E.
- Venue
- Nature
- Published
- 2015-03-18
- Volume
- 521
- Issue
- 7552
- Pages
- 366-370
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2072153595
- Cited by
- 375
- References
- 38
- FWCI
- 19.56
- Type
- journal article
- Language
- en
- Open access
- green
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