IRF2 is a master regulator of human keratinocyte stem cell fate

• DOI: 10.1038/s41467-019-12559-x
• Publication Date: 2019-10-14T10:03:51Z
• Authors: Nicolas Mercado; Gabi Schutzius; Christian Kolter; David Estoppey; Sebastian Bergling; Guglielmo Roma; Caroline Gubser K...; Florian Nigsch; Adrian Salathe; Remi Terranova; John Reece-Hoyes; John Alford; Carsten Russ; Judith Knehr; Dominic Hoepfner; Alexandra Aebi; Heinz Ruffner; Tanner C. Beck; Sajjeev Jagannathan; Calla M. Olson; Hadley E. Sheppard; Selma Z. Elsarrag; Tewis Bouwmeester; Mathias Frederiksen; Felix Lohmann; Charles Y. Lin; Susan Kirkland
• Keywords: Cell fate determination

Abstract Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic intrinsic regulation. Transcription factor-controlled regulatory circuitries govern identity, are sufficient to induce pluripotency transdifferentiate cells. We investigate whether transcriptional circuitry also governs phenotypic changes within a given type comparing primary with intrinsically high versus low potential. Using integrated chromatin profiling, we implicate IRF2 as antagonistic stemness show that it binds regulates active cis -regulatory elements at interferon response antigen presentation genes. CRISPR-KD increases self-renewal, migration epidermis formation. These data demonstrate transcription factor circuitries, addition maintaining control plasticity types offer for therapeutic modulation function.