Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

Rene C. Adam, Hanseul Yang, Shira Rockowitz, Samantha B. Larsen, Maria Nikolova, Daniel S. Oristian, Lisa Polak, Meelis Kadaja, Amma Asare, Deyou Zheng, Elaine Fuchs

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)366-370
Number of pages5
JournalNature
Volume521
Issue number7552
DOIs
StatePublished - May 21 2015

Fingerprint

Hair Follicle
Cell Lineage
Stem Cells
Adult Stem Cells
Chromatin
Transcription Factors
Wounds and Injuries
Stem Cell Transplantation
Homeostasis
Binding Sites
Cell Plasticity
Genes

ASJC Scopus subject areas

  • General

Cite this

Adam, R. C., Yang, H., Rockowitz, S., Larsen, S. B., Nikolova, M., Oristian, D. S., ... Fuchs, E. (2015). Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature, 521(7552), 366-370. https://doi.org/10.1038/nature14289

Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. / Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine.

In: Nature, Vol. 521, No. 7552, 21.05.2015, p. 366-370.

Research output: Contribution to journalArticle

Adam, RC, Yang, H, Rockowitz, S, Larsen, SB, Nikolova, M, Oristian, DS, Polak, L, Kadaja, M, Asare, A, Zheng, D & Fuchs, E 2015, 'Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice', Nature, vol. 521, no. 7552, pp. 366-370. https://doi.org/10.1038/nature14289
Adam RC, Yang H, Rockowitz S, Larsen SB, Nikolova M, Oristian DS et al. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature. 2015 May 21;521(7552):366-370. https://doi.org/10.1038/nature14289
Adam, Rene C. ; Yang, Hanseul ; Rockowitz, Shira ; Larsen, Samantha B. ; Nikolova, Maria ; Oristian, Daniel S. ; Polak, Lisa ; Kadaja, Meelis ; Asare, Amma ; Zheng, Deyou ; Fuchs, Elaine. / Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. In: Nature. 2015 ; Vol. 521, No. 7552. pp. 366-370.
@article{34f4264142474c02b7cb4cf87397e3ea,
title = "Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice",
abstract = "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.",
author = "Adam, {Rene C.} and Hanseul Yang and Shira Rockowitz and Larsen, {Samantha B.} and Maria Nikolova and Oristian, {Daniel S.} and Lisa Polak and Meelis Kadaja and Amma Asare and Deyou Zheng and Elaine Fuchs",
year = "2015",
month = "5",
day = "21",
doi = "10.1038/nature14289",
language = "English (US)",
volume = "521",
pages = "366--370",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7552",

}

TY - JOUR

T1 - Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

AU - Adam, Rene C.

AU - Yang, Hanseul

AU - Rockowitz, Shira

AU - Larsen, Samantha B.

AU - Nikolova, Maria

AU - Oristian, Daniel S.

AU - Polak, Lisa

AU - Kadaja, Meelis

AU - Asare, Amma

AU - Zheng, Deyou

AU - Fuchs, Elaine

PY - 2015/5/21

Y1 - 2015/5/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929211885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929211885&partnerID=8YFLogxK

U2 - 10.1038/nature14289

DO - 10.1038/nature14289

M3 - Article

VL - 521

SP - 366

EP - 370

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7552

ER -