Sox10 Regulates Plasticity of Epithelial Progenitors toward Secretory Units of Exocrine Glands

Abstract

SummaryUnderstanding how epithelial progenitors within exocrine glands establish specific cell lineages and form complex functional secretory units is vital for organ regeneration. Here we identify the transcription factor Sox10 as essential for both the maintenance and differentiation of epithelial KIT+FGFR2b+ progenitors into secretory units, containing acinar, myoepithelial, and intercalated duct cells. The KIT/FGFR2b-Sox10 axis marks the earliest multi-potent and tissue-specific progenitors of exocrine glands. Genetic deletion of epithelial Sox10 leads to loss of secretory units, which reduces organ size and function, but the ductal tree is retained. Intriguingly, the remaining duct progenitors do not compensate for loss of Sox10 and lack plasticity to properly form secretory units. However, overexpression of Sox10 in these ductal progenitors enhances their plasticity toward KIT+ progenitors and induces differentiation into secretory units. Therefore, Sox10 controls plasticity and multi-potency of epithelial KIT+ cells in secretory organs, such as mammary, lacrimal, and salivary glands.

CERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands

“…DeSeq2 was used to performed statistical test analysis to assess differential gene expression (DGE) between groups with a log2 fold in expression with the adjusted p value of <0.05, as previously described in Athwal et al. 41 RNA-seq data are available on the Gene Expression Omnibus (GEO) website (GEO: GSE150112 ).…”

Functional specialization of human salivary glands and origins of proteins intrinsic to human saliva

“…Our analysis identified a host of TFs previously shown through genetic deletion studies in mice to be essential regulators of salivary gland development to be also universally expressed in the developing human glands. These include regulators of acinar cell development (e.g., SOX2, 9 and 10 (Athwal et al, 2019;Chatzeli et al, 2017;Emmerson et al, 2017) ), targets of FGF10 signaling (e.g., ETV5 ), regulators of duct formation ( TFCP2L1 (Yamaguchi et al, 2006) and YAP1 (Szymaniak et al, 2017) ) and of basal stem cells ( TP63 (Song et al, 2018) ), and a TF recently discovered to promote salivary organoid initiation from mouse embryonic stem cells ( FOXC1 (Tanaka et al, 2018) ). Notably, a group of TFs including FOXD3, CBX2, and SOX11…”

3D Organoid Formation from the Murine Salivary Gland Cell Line SIMS

“…Although adult acinar and myoepithelial cells were found in vivo to preserve their own cell population through self-duplication ( conditions. Our recent work shows that SIMS cells have the ability to differentiate into unique populations of acinar, myoepithelial, and duct cells in 3D differentiation conditions, that normally produce, modify and secrete saliva in vivo (Lombaert et al, 2011;Athwal et al, 2019). This protocol describes the workflow necessary for the generation and analysis of 3D differentiated SIMS cells.…”

“…These organoids are also stained either via cryosectioning or in 3D to analyze for differentiation markers and cell populations. Alterations, such as cell transfections, transductions and/or media changes, to this condition can easily be made to address specific research questions (Athwal et al, 2019). The media components were adjusted using literature from both existing salivary and mammary gland differentiation protocols, which deemed necessary to induce differentiation of the SIMS cells in vitro.…”

“…This staining can also be performed on cryosections of OCT embedded organoid matrix (Athwal et al, 2019). A complete description of the Scale bar, 10 μm.…”