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

iScience

Monika Che¹  Rose-Anne Romano²  Christian Gluck²  Satrajit Sinha³  Elsa Flores⁴  Akinsola Oyelakin⁴  Eun-Ah Christine Song⁴  Kirsten Smalley⁴  Sangwon Min⁴  Jonathan E. Bard⁵ 

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

关键词: Cell Biology;    Developmental Biology;    Stem Cells Research;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown