High-Resolution Transcriptomic Landscape of the Human Submandibular Gland

Horeth, Erich; Bard, Jonathan; Che, Monika; Wrynn, Theresa; Song, Eun Kyeung; Marzullo, Brandon; Burke, Mark S.; Popat, Saurin R.; Loree, Thom R.; Zemer, James; Tapia, José Luís; Frustino, Jennifer; Kramer, Jill M.; Sinha, Satrajit; Romano, Rose‐Anne

doi:10.1177/00220345221147908

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…An additional possibility is that the ID cells may differentially secrete a complement of proteins. For example, in a recent study examining the transcriptome of the human submandibular gland, numerous transcripts for secreted proteins involved in inflammation were enriched in the ID cells (Horeth et al., 2023). Overall, these data may indicate that the IDs play an important role in oral immune defence.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype

Wahl,

Takano,

et al. 2023

The Journal of Physiology

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Currently, all salivary ducts (intercalated, striated and collecting) are assumed to function broadly in a similar manner, reclaiming ions that were secreted by the secretory acinar cells while preserving fluid volume and delivering saliva to the oral cavity. Nevertheless, there has been minimal investigation into the structural and functional differences between distinct types of salivary duct cells. Therefore, in this study, the expression profile of proteins involved in stimulus–secretion coupling, as well as the function of the intercalated duct (ID) and striated duct cells, was examined. Particular focus was placed on defining differences between distinct duct cell populations. To accomplish this, immunohistochemistry and in situ hybridization were utilized to examine the localization and expression of proteins involved in reabsorption and secretion of ions and fluid. Further, in vivo calcium imaging was employed to investigate cellular function. Based on the protein expression profile and functional data, marked differences between the IDs and striated ducts were observed. Specifically, the ID cells express proteins native to the secretory acinar cells while lacking proteins specifically expressed in the striated ducts. Further, the ID and striated duct cells display different calcium signalling characteristics, with the IDs responding to a neural stimulus in a manner similar to the acinar cells. Overall, our data suggest that the IDs have a distinct role in the secretory process, separate from the reabsorptive striated ducts. Instead, based on our evidence, the IDs express proteins found in secretory cells, generate calcium signals in a manner similar to acinar cells, and, therefore, are likely secretory cells. imageKey points Current studies examining salivary intercalated duct cells are limited, with minimal documentation of the ion transport machinery and the overall role of the cells in fluid generation. Salivary intercalated duct cells are presumed to function in the same manner as other duct cells, reclaiming ions, maintaining fluid volume and delivering the final saliva to the oral cavity. Here we systematically examine the structure and function of the salivary intercalated duct cells using immunohistochemistry, in situ hybridization and by monitoring in vivo Ca2+ dynamics. Structural data revealed that the intercalated duct cells lack proteins vital for reabsorption and express proteins necessary for secretion. Ca2+ dynamics in the intercalated duct cells were consistent with those observed in secretory cells and resulted from GPCR‐mediated IP3 production.

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Section: Discussionmentioning

confidence: 99%

Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype

Wahl,

Takano,

et al. 2023

The Journal of Physiology

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“…A toolkit CellChat used to quantitatively infer and analyze intercellular communication networks from scRNA-seq data ( 28 ). It is based on the database of interactions among ligands, receptors and their cofactors.…”

Section: Methodsmentioning

confidence: 99%

Comparative analysis of single-cell transcriptome reveals heterogeneity and commonality in the immune microenvironment of colorectal cancer and inflammatory bowel disease

Lv,

Mu,

Zhang

et al. 2024

Front. Immunol.

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BackgroundDuring aging, chronic inflammation can promote tumor development and metastasis. Patients with chronic inflammatory bowel diseases (IBD) are at an increased risk of developing colorectal cancer (CRC). However, the molecular mechanism underlying is still unclear.MethodsWe conducted a large-scale single-cell sequencing analysis comprising 432,314 single cells from 92 CRC and 24 IBD patients. The analysis focused on the heterogeneity and commonality of CRC and IBD with respect to immune cell landscape, cellular communication, aging and inflammatory response, and Meta programs.ResultsThe CRC and IBD had significantly different propensities in terms of cell proportions, differential genes and their functions, and cellular communication. The progression of CRC was mainly associated with epithelial cells, fibroblasts, and monocyte-macrophages, which displayed pronounced metabolic functions. In particular, monocyte-macrophages were enriched for the aging and inflammation-associated NF-κB pathway. And IBD was enriched in immune-related functions with B cells and T cells. Cellular communication analysis in CRC samples displayed an increase in MIF signaling from epithelial cells to T cells, and an increase in the efferent signal of senescence-associated SPP1 signaling from monocyte-macrophages. Notably, we also found some commonalities between CRC and IBD. The efferent and afferent signals showed that the pro-inflammatory cytokine played an important role. And the activity of aging and inflammatory response with AUCell analysis also showed a high degree of commonality. Furthermore, using the Meta programs (MPs) with the NMF algorithm, we found that the CRC non-malignant cells shared a substantial proportion of the MP genes with CRC malignant cells (68% overlap) and IBD epithelial cells (52% overlap), respectively. And it was extensively involved in functions of cell cycle and immune response, revealing its dual properties of inflammation and cancer. In addition, CRC malignant and non-malignant cells were enriched for the senescence-related cell cycle G2M phase transition and the p53 signaling pathway.ConclusionOur study highlights the characteristics of aging, inflammation and tumor in CRC and IBD at the single-cell level, and the dual property of inflammation-cancer in CRC non-malignant cells may provide a more up-to-date understanding of disease transformation.

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“…Our findings reveal a remarkably conserved cytokeratin profile in salivary glands across mammalian species, enabling the identification of rare primitive cells. Utilizing comprehensive keratin profiling via single cell proteomics and scRNA-seq, we present compelling evidence indicating intricate developmental interconnections among ductal basal and acinar myoepithelial cells, potentially exhibiting niche-specific functions 46 . Moreover, our data suggests that a rare subset of scattered basal cells within ducts, similar to mammary gland, may harbor more primitive functionalities, accessible through our in vitro culture conditions, which are vital for future studies 47 .…”

Section: Single-cell Proteomics Identifies Putative Origin Of Primiti...mentioning

confidence: 99%

The Mayo Clinic Salivary Tissue-Organoid Biobanking: A Resource for Salivary Regeneration Research

Aalam,

Varela,

Khaderi

et al. 2024

Preprint

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The salivary gland (SG) is an essential organ that secretes saliva, which supports versatile oral function throughout life, and is maintained by elusive epithelial stem and progenitor cells (SGSPC). Unfortunately, aging, drugs, autoimmune disorders, and cancer treatments can lead to salivary dysfunction and associated health consequences. Despite many ongoing therapeutic efforts to mediate those conditions, investigating human SGSPC is challenging due to lack of standardized tissue collection, limited tissue access, and inadequate purification methods. Herein, we established a diverse and clinically annotated salivary regenerative biobanking at the Mayo Clinic, optimizing viable salivary cell isolation and clonal assays in both 2D and 3D-matrigel growth environments. Our analysis identified ductal epithelial cells in vitro enriched with SGSPC expressing the CD24/EpCAM/CD49f+ and PSMA- phenotype. We identified PSMA expression as a reliable SGSPC differentiation marker. Moreover, we identified progenitor cell types with shared phenotypes exhibiting three distinct clonal patterns of salivary differentiation in a 2D environment. Leveraging innovative label-free unbiased LC-MS/MS-based single-cell proteomics, we identified 819 proteins across 71 single cell proteome datasets from purified progenitor-enriched parotid gland (PG) and sub-mandibular gland (SMG) cultures. We identified distinctive co-expression of proteins, such as KRT1/5/13/14/15/17/23/76 and 79, exclusively observed in rare, scattered salivary ductal basal cells, indicating the potential de novo source of SGSPC. We also identified an entire class of peroxiredoxin peroxidases, enriched in PG than SMG, and attendant H2O2-dependent cell proliferation in vitro suggesting a potential role for PRDX-dependent floodgate oxidative signaling in salivary homeostasis. The distinctive clinical resources and research insights presented here offer a foundation for exploring personalized regenerative medicine.

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High-Resolution Transcriptomic Landscape of the Human Submandibular Gland

Cited by 9 publications

References 37 publications

Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype

Structural and functional analysis of salivary intercalated duct cells reveals a secretory phenotype

Comparative analysis of single-cell transcriptome reveals heterogeneity and commonality in the immune microenvironment of colorectal cancer and inflammatory bowel disease

The Mayo Clinic Salivary Tissue-Organoid Biobanking: A Resource for Salivary Regeneration Research

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