p63 and Its Target Follistatin Maintain Salivary Gland Stem/Progenitor Cell Function through TGF-β/Activin Signaling
| Autor: | Eun-Ah Christine Song, Akinsola Oyelakin, Rose-Anne Romano, Sangwon Min, Satrajit Sinha, Elsa R. Flores, Christian Gluck, Monika Che, Jonathan E. Bard, Kirsten Smalley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
education.field_of_study
Multidisciplinary biology Cellular differentiation Population Cell Cell Biology Cell fate determination Embryonic stem cell Article Cell biology medicine.anatomical_structure Cistrome Stem Cells Research biology.protein medicine lcsh:Q Progenitor cell education lcsh:Science Follistatin Developmental Biology |
| Zdroj: | iScience, Vol 23, Iss 9, Pp 101524-(2020) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary Multipotent ΔNp63-positive cells maintain all epithelial cell lineages of the embryonic and adult salivary gland (SG). However, the molecular mechanisms by which ΔNp63 regulates stem/progenitor (SP) cell populations in the SG remains elusive. To understand the role of ΔNp63 in directing cell fate choices in this gland, we have generated ΔNp63-deleted adult mice and primary salivary cell cultures to probe alterations in SP cell differentiation and function. In parallel, we have leveraged RNA-seq and ChIP-seq-based characterization of the ΔNp63-driven cistrome and scRNA-seq analysis to molecularly interrogate altered SG cellular identities and differentiation states dependent on ΔNp63. Our studies reveal that ablation of ΔNp63 results in a loss of the SP cell population and skewed differentiation that is mediated by Follistatin-dependent dysregulated TGF-β/Activin signaling. These findings offer new revelations into the SP cell gene regulatory networks that are likely to be relevant for normal or diseased SG states. Graphical Abstract Highlights • Loss of ΔNp63 expression results in a block in salivary gland cell differentiation • p63 maintains salivary gland stem and progenitor cell proliferation • p63 acts upstream of TGF-β/Activin signaling by directly regulating Fst expression Cell Biology; Developmental Biology; Stem Cells Research |
| Databáze: | OpenAIRE |
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