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When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light

by 1,2,3,4,* and 1,2,3,4,*
1
Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, Institut de Biologie François Jacob, CEA/DRF, Institut de Radiobiologie Cellulaire et Moléculaire, 91000 Evry, France
2
INSERM U967, 92260 Fontenay-aux-Roses, France
3
Université Paris-Saclay, 91190 Saint-Aubin, France
4
Université Paris-Diderot, 75013 Paris, France
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(10), 2188; https://doi.org/10.3390/cells9102188
Received: 27 August 2020 / Revised: 24 September 2020 / Accepted: 25 September 2020 / Published: 28 September 2020
(This article belongs to the Special Issue Feature Papers in Stem Cells)
The transcription factor “Kruppel-like factor 4” (KLF4) is a central player in the field of pluripotent stem cell biology. In particular, it was put under the spotlight as one of the four factors of the cocktail originally described for reprogramming into induced pluripotent stem cells (iPSCs). In contrast, its possible functions in native tissue stem cells remain largely unexplored. We recently published that KLF4 is a regulator of “stemness” in human keratinocytes. We show that reducing the level of expression of this transcription factor by RNA interference or pharmacological repression promotes the ex vivo amplification and regenerative capacity of two types of cells of interest for cutaneous cell therapy: native keratinocyte stem and progenitor cells from adult epidermis, which have been used for more than three decades in skin graft bioengineering, and keratinocytes generated by the lineage-oriented differentiation of embryonic stem cells (ESCs), which have potential for the development of skin bio-bandages. At the mechanistic level, KLF4 repression alters the expression of a large set of genes involved in TGF-β1 and WNT signaling pathways. Major regulators of TGF-β bioavailability and different TGF-β receptors were targeted, notably modulating the ALK1/Smad1/5/9 axis. At a functional level, KLF4 repression produced an antagonist effect on TGF-β1-induced keratinocyte differentiation. View Full-Text
Keywords: KLF4; adult epidermal keratinocytes; ESC-derived keratinocytes; stemness; skin grafts; TGF-β1; WNT KLF4; adult epidermal keratinocytes; ESC-derived keratinocytes; stemness; skin grafts; TGF-β1; WNT
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MDPI and ACS Style

Fortunel, N.O.; Martin, M.T. When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light. Cells 2020, 9, 2188. https://doi.org/10.3390/cells9102188

AMA Style

Fortunel NO, Martin MT. When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light. Cells. 2020; 9(10):2188. https://doi.org/10.3390/cells9102188

Chicago/Turabian Style

Fortunel, Nicolas O., and Michèle T. Martin 2020. "When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light" Cells 9, no. 10: 2188. https://doi.org/10.3390/cells9102188

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