IRF2 is a master regulator of human keratinocyte stem cell fate
| العنوان: | IRF2 is a master regulator of human keratinocyte stem cell fate |
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| المؤلفون: | Carsten Russ, Adrian Salathe, Charles Y. Lin, John Alford, Mathias Frederiksen, Caroline Gubser Keller, Gabi Schutzius, Sajjeev Jagannathan, Sebastian Bergling, Dominic Hoepfner, Heinz Ruffner, Nicolas Mercado, Judith Knehr, Alexandra Aebi, John S. Reece-Hoyes, Guglielmo Roma, David Estoppey, Remi Terranova, Hadley E. Sheppard, Calla M. Olson, Tewis Bouwmeester, Tanner C. Beck, Susan Kirkland, Florian Nigsch, Christian Kolter, Felix Lohmann, Selma Z. Elsarrag |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Keratinocytes, Transcriptional Activation, 0301 basic medicine, Cell type, Science, Antigen presentation, General Physics and Astronomy, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Gene regulatory networks, 03 medical and health sciences, 0302 clinical medicine, Interferon, Transcription (biology), medicine, Humans, Regeneration, lcsh:Science, Transcription factor, Tissue homeostasis, Multidisciplinary, Stem Cells, Cell Differentiation, General Chemistry, Cell biology, Chromatin, 030104 developmental biology, Self-renewal, lcsh:Q, Stem cell, Interferon Regulatory Factor-2, 030217 neurology & neurosurgery, Transcription Factors, Skin stem cells, medicine.drug |
| الوصف: | Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The stem cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic and intrinsic regulation. Transcription factor-controlled regulatory circuitries govern cell identity, are sufficient to induce pluripotency and transdifferentiate cells. We investigate whether transcriptional circuitry also governs phenotypic changes within a given cell type by comparing human primary keratinocytes with intrinsically high versus low stem cell potential. Using integrated chromatin and transcriptional profiling, we implicate IRF2 as antagonistic to stemness and show that it binds and regulates active cis-regulatory elements at interferon response and antigen presentation genes. CRISPR-KD of IRF2 in keratinocytes with low stem cell potential increases self-renewal, migration and epidermis formation. These data demonstrate that transcription factor regulatory circuitries, in addition to maintaining cell identity, control plasticity within cell types and offer potential for therapeutic modulation of cell function. Epidermal homeostasis requires long term stem cell function. Here, the authors apply transcriptional circuitry analysis based on integrated epigenomic profiling of primary human keratinocytes with high and low stem cell function to identify IRF2 as a negative regulator of stemness. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31c9ef08e8616e1ba4a2ab8d68197bb3 http://link.springer.com/article/10.1038/s41467-019-12559-x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....31c9ef08e8616e1ba4a2ab8d68197bb3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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