Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4

Nuno Miguel Luis, LLuis Morey, Stefania Mejetta, Gloria Pascual, Peggy Janich, Bernd Kuebler, Guglielmo Roma, Elisabete Nascimento, Michaela Frye, Luciano Di Croce, Salvador Aznar Benitah

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex 1 (PRC1)-associated protein, maintains human epidermal stem cells as slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its antisenescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors such as Ezh2, Dnmt1, and Bmi1 to prevent the active stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation.

Original languageEnglish (US)
Pages (from-to)233-246
Number of pages14
JournalCell Stem Cell
Volume9
Issue number3
DOIs
StatePublished - Sep 2 2011
Externally publishedYes

Fingerprint

Cell Aging
Stem Cells
Cell Proliferation
Polycomb Repressive Complex 1
Cell Differentiation
Homeostasis
Ligases
Transcriptome
Epidermis
Chromatin
Cell Cycle
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4. / Luis, Nuno Miguel; Morey, LLuis; Mejetta, Stefania; Pascual, Gloria; Janich, Peggy; Kuebler, Bernd; Roma, Guglielmo; Nascimento, Elisabete; Frye, Michaela; Di Croce, Luciano; Benitah, Salvador Aznar.

In: Cell Stem Cell, Vol. 9, No. 3, 02.09.2011, p. 233-246.

Research output: Contribution to journalArticle

Luis, NM, Morey, LL, Mejetta, S, Pascual, G, Janich, P, Kuebler, B, Roma, G, Nascimento, E, Frye, M, Di Croce, L & Benitah, SA 2011, 'Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4', Cell Stem Cell, vol. 9, no. 3, pp. 233-246. https://doi.org/10.1016/j.stem.2011.07.013
Luis, Nuno Miguel ; Morey, LLuis ; Mejetta, Stefania ; Pascual, Gloria ; Janich, Peggy ; Kuebler, Bernd ; Roma, Guglielmo ; Nascimento, Elisabete ; Frye, Michaela ; Di Croce, Luciano ; Benitah, Salvador Aznar. / Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4. In: Cell Stem Cell. 2011 ; Vol. 9, No. 3. pp. 233-246.
@article{ab2b1577b5d44d938cf4471d4403154a,
title = "Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4",
abstract = "Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex 1 (PRC1)-associated protein, maintains human epidermal stem cells as slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its antisenescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors such as Ezh2, Dnmt1, and Bmi1 to prevent the active stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation.",
author = "Luis, {Nuno Miguel} and LLuis Morey and Stefania Mejetta and Gloria Pascual and Peggy Janich and Bernd Kuebler and Guglielmo Roma and Elisabete Nascimento and Michaela Frye and {Di Croce}, Luciano and Benitah, {Salvador Aznar}",
year = "2011",
month = "9",
day = "2",
doi = "10.1016/j.stem.2011.07.013",
language = "English (US)",
volume = "9",
pages = "233--246",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Regulation of human epidermal stem cell proliferation and senescence requires polycomb-dependent and independent functions of cbx4

AU - Luis, Nuno Miguel

AU - Morey, LLuis

AU - Mejetta, Stefania

AU - Pascual, Gloria

AU - Janich, Peggy

AU - Kuebler, Bernd

AU - Roma, Guglielmo

AU - Nascimento, Elisabete

AU - Frye, Michaela

AU - Di Croce, Luciano

AU - Benitah, Salvador Aznar

PY - 2011/9/2

Y1 - 2011/9/2

N2 - Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex 1 (PRC1)-associated protein, maintains human epidermal stem cells as slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its antisenescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors such as Ezh2, Dnmt1, and Bmi1 to prevent the active stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation.

AB - Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex 1 (PRC1)-associated protein, maintains human epidermal stem cells as slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its antisenescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors such as Ezh2, Dnmt1, and Bmi1 to prevent the active stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation.

UR - http://www.scopus.com/inward/record.url?scp=80052300618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052300618&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2011.07.013

DO - 10.1016/j.stem.2011.07.013

M3 - Article

C2 - 21885019

AN - SCOPUS:80052300618

VL - 9

SP - 233

EP - 246

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 3

ER -