p63 and Its Target Follistatin Maintain Salivary Gland Stem/Progenitor Cell Function through TGF-β/Activin Signaling

Sangwon Min; Akinsola Oyelakin; Christian Gluck; Jonathan E Bard; Eun-Ah Christine Song; Kirsten Smalley; Monika Che; Elsa Flores; Satrajit Sinha; Rose-Anne Romano

doi:10.1016/j.isci.2020.101524

p63 and Its Target Follistatin Maintain Salivary Gland Stem/Progenitor Cell Function through TGF-β/Activin Signaling

iScience. 2020 Sep 2;23(9):101524. doi: 10.1016/j.isci.2020.101524. eCollection 2020 Sep 25.

Authors

Affiliations

¹ Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA.
² Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USA.
³ Genomics and Bioinformatics Core, State University of New York at Buffalo, Buffalo, NY 14203, USA.
⁴ Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Abstract

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.

Keywords: Cell Biology; Developmental Biology; Stem Cells Research.

Abstract

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