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Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties

Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties
Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6+ cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

Animals, Cell Dedifferentiation, Cell Lineage, Cell Movement, Cell Plasticity, Cell Self Renewal, Cells, Cultured, Disease Models, Animal, Epidermis/metabolism, Female, GATA6 Transcription Factor/deficiency, Male, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Positive Regulatory Domain I-Binding Factor 1, Sebaceous Glands/metabolism, Signal Transduction, Stem Cells/metabolism, Time Factors, Transcription Factors/genetics, Wound Healing, Wounds and Injuries/genetics
1465-7392
603-613
Donati, Giacomo
e4d333d5-9fd8-44a4-8f8b-98f40fb0cc2c
Rognoni, Emanuel
e180c550-fc77-434b-b0c0-2c1190a28ae7
Hiratsuka, Toru
a7a5a3ff-506f-4c68-9af5-9ed0c5d7d55b
Liakath-Ali, Kifayathullah
8d5a020c-e976-4901-9195-68f4bc0de74e
Hoste, Esther
75d99ab6-7b2d-4ed8-b6c8-d5c7569734c7
Kar, Gozde
08c561f2-3a2b-4cab-b41e-e9147a3f709f
Kayikci, Melis
c6e727a9-c4a1-4b94-86ac-6a428f8037b5
Russell, Roslin
41eb930f-4483-44c6-997c-e739072c7811
Kretzschmar, Kai
3b033c36-f49f-490d-afb4-2f9b99f3319f
Mulder, Klaas W.
f3895885-b7c3-476c-82a4-cd07bec55327
Teichmann, Sarah A.
e72b3afe-69c5-46f5-a47c-ec53edd23a52
Watt, Fiona M.
24fff937-94b0-4127-8cbb-e8bd6e01fa29
Donati, Giacomo
e4d333d5-9fd8-44a4-8f8b-98f40fb0cc2c
Rognoni, Emanuel
e180c550-fc77-434b-b0c0-2c1190a28ae7
Hiratsuka, Toru
a7a5a3ff-506f-4c68-9af5-9ed0c5d7d55b
Liakath-Ali, Kifayathullah
8d5a020c-e976-4901-9195-68f4bc0de74e
Hoste, Esther
75d99ab6-7b2d-4ed8-b6c8-d5c7569734c7
Kar, Gozde
08c561f2-3a2b-4cab-b41e-e9147a3f709f
Kayikci, Melis
c6e727a9-c4a1-4b94-86ac-6a428f8037b5
Russell, Roslin
41eb930f-4483-44c6-997c-e739072c7811
Kretzschmar, Kai
3b033c36-f49f-490d-afb4-2f9b99f3319f
Mulder, Klaas W.
f3895885-b7c3-476c-82a4-cd07bec55327
Teichmann, Sarah A.
e72b3afe-69c5-46f5-a47c-ec53edd23a52
Watt, Fiona M.
24fff937-94b0-4127-8cbb-e8bd6e01fa29

Donati, Giacomo, Rognoni, Emanuel, Hiratsuka, Toru, Liakath-Ali, Kifayathullah, Hoste, Esther, Kar, Gozde, Kayikci, Melis, Russell, Roslin, Kretzschmar, Kai, Mulder, Klaas W., Teichmann, Sarah A. and Watt, Fiona M. (2017) Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties. Nature Cell Biology, 19 (6), 603-613. (doi:10.1038/ncb3532).

Record type: Article

Abstract

The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6+ cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue. Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane. This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.

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More information

Accepted/In Press date: 18 April 2017
e-pub ahead of print date: 15 May 2017
Published date: 1 June 2017
Keywords: Animals, Cell Dedifferentiation, Cell Lineage, Cell Movement, Cell Plasticity, Cell Self Renewal, Cells, Cultured, Disease Models, Animal, Epidermis/metabolism, Female, GATA6 Transcription Factor/deficiency, Male, Mice, Inbred C57BL, Mice, Knockout, Phenotype, Positive Regulatory Domain I-Binding Factor 1, Sebaceous Glands/metabolism, Signal Transduction, Stem Cells/metabolism, Time Factors, Transcription Factors/genetics, Wound Healing, Wounds and Injuries/genetics

Identifiers

Local EPrints ID: 491580
URI: http://eprints.soton.ac.uk/id/eprint/491580
ISSN: 1465-7392
PURE UUID: 9686a2d2-ab7a-4e71-8990-af769b653d9c
ORCID for Kifayathullah Liakath-Ali: ORCID iD orcid.org/0000-0001-9047-7424

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Date deposited: 27 Jun 2024 16:37
Last modified: 28 Jun 2024 02:09

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Contributors

Author: Giacomo Donati
Author: Emanuel Rognoni
Author: Toru Hiratsuka
Author: Kifayathullah Liakath-Ali ORCID iD
Author: Esther Hoste
Author: Gozde Kar
Author: Melis Kayikci
Author: Roslin Russell
Author: Kai Kretzschmar
Author: Klaas W. Mulder
Author: Sarah A. Teichmann
Author: Fiona M. Watt

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