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
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.
