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IRF2 is a master regulator of human keratinocyte stem cell fate

Mercado, Nicolas and Schutzius, Gabi and Hauer, Christian and Estoppey, David and Bergling, Sebastian and Roma, Guglielmo and Gubser Keller, Caroline and Nigsch, Florian and Salathe, Adrian and Terranova, Remi and Reece-Hoyes, John and Knehr, Judith and Hoepfner, Dominic and Aebi, Alexandra and Ruffner, Heinz and Russ, Carsten and Bouwmeester, Antonius and Frederiksen, Mathias and Lohmann, Felix and Kirkland, Susan and Lin , Charles Y and Beck, Tanner (2019) IRF2 is a master regulator of human keratinocyte stem cell fate. Nature communications, 10 (Articl). ISSN 41467-019-12559-x

Abstract

SUMMARY
Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and provision of differentiated cells. Human epidermal keratinocytes retain stem cell potential in vitro but this is highly variable and lost over time suggesting extrinsic and intrinsic regulation.
As transcription factor regulatory circuits have been shown to govern cell identity and are sufficient to induce pluripotency or transdifferentiate cell types, we sought to define changes in transcriptional circuitry between two populations of keratinocytes with intrinsic high and low stem cell potential.
Using integrated chromatin and transcriptional profiling, we implicate the transcription factor IRF2 as antagonistic to stemness and show that its knockdown in keratinocytes with low stem cell potential is sufficient to increase self-renewal, migration and ability to generate 3D human skin constructs.
These data suggest that transcription factor regulatory circuits, in addition to maintaining cell identity, control cellular plasticity and could offer potential for therapeutic modulation of cell function

Item Type: Article
Keywords: Epidermal Stem cell fate, adult stem cell, skin biology, regenerative medicine
Date Deposited: 30 Oct 2019 00:45
Last Modified: 30 Oct 2019 00:45
URI: https://oak.novartis.com/id/eprint/37563

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