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

iScience (Sep 2020)

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

Affiliations

Sangwon Min: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA
Akinsola Oyelakin: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA
Christian Gluck: Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USA
Jonathan E. Bard: Genomics and Bioinformatics Core, State University of New York at Buffalo, Buffalo, NY 14203, USA
Eun-Ah Christine Song: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA
Kirsten Smalley: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USA
Monika Che: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA
Elsa Flores: Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Satrajit Sinha: Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USA
Rose-Anne Romano: Department of Oral Biology, State University of New York at Buffalo, School of Dental Medicine, 3435 Main Street, Buffalo, NY 14214, USA; Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY 14203, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 9
p. 101524

Abstract

Read online

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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords