Dataset Information

Establishment of Salivary Tissue-Organoid Biorepository

ABSTRACT: The salivary gland plays a crucial role in oral function and overall health by secreting saliva, yet salivary dysfunction due to aging, medications, autoimmune disorders, and cancer treatments poses significant challenges. We established the first diverse and clinically annotated salivary regenerative biobank at Mayo Clinic to study salivary gland stem/progenitor cells (SGSPCs). Optimization of cell isolation and progenitor assays revealed SGSPCs enriched within the CD24/EpCAM/CD49f+ and PSMA- phenotype of both submandibular and parotid glands, with clonal differentiation assays highlighting heterogeneity. Induction of PSMA/FOLH1 expression was associated with SGSPC differentiation. Utilizing label-free single-cell proteomics, we identified 819 unique proteins in SGSPC-enriched cells, including co-expressed cytokeratins, expressed in rare salivary ductal basal cells. Additionally, PRDX, a unique class of peroxiredoxin peroxidases enriched in SGSPCs demonstrated H2O2-dependent growth, suggesting a role in salivary homeostasis. These findings lay a solid foundation for studying SGSPCs and may lead to personalized regenerative medicine for salivary gland dysfunction.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

SUBMITTER: Akhilesh Pandey

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD055869 | Pride | 2025-05-26

REPOSITORIES: Pride

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Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1.

Aalam Syed Mohammed Musheer SMM Varela Ana Rita AR Khaderi Aalim A Mondesir Ronsard J RJ Mun Dong-Gi DG Ding Andrew A Lombaert Isabelle M A IMA Coppes Rob P RP Emperumal Chitra Priya CP Pandey Akhilesh A Janus Jeffrey R JR Kannan Nagarajan N

NPJ Regenerative medicine 20250521 1

The salivary gland (SG) is vital for oral function and overall health through secretion of saliva. However salivary dysfunction due to aging, medications, autoimmune disorders, and cancer treatments poses significant challenges. We established the first diverse and clinically annotated salivary regenerative biobank at Mayo Clinic to study salivary gland stem/progenitor cells (SGSPCs). Optimization of cell isolation and progenitor assays revealed SGSPCs enriched within the CD24/EpCAM/CD49f+ and P ...[more]

PMID: 40399315

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Project description:Radiotherapy of head and neck cancer is accompanied by unavoidable co-irradiation of the salivary gland, often resulting in hyposalivation and reduced quality of life. Irradiated salivary gland tissue is characterized by the presence of cellular senescence, fibrosis, and a chronic inflammatory state changing the cellular microenvironment. These microenvironmental changes may be unfavorable for the regenerative potential of tissue stem cells inhibiting regenerative medicine options. Therefore, we investigated microenvironmental changes of the irradiated murine salivary gland and their effect on the potency of salivary gland stem/progenitor cells (SGSCs). After 15 Gy local irradiation of murine salivary glands, alongside an in time advancing decline in function, the submandibular gland (SMG) showed extensive fibrosis, p21-expressing senescent cells, and immune cell infiltration, all indicative of microenvironmental changes. Additionally, irradiated SMG contained a lower number of CD24++/CD29++ and CD24++/CD29+ stem/progenitor cell enrichment marker-expressing cells 30 days post-irradiation which coincides with a reduction in salisphere formation potential over time. However, after subsequent passaging of organoids derived from glands obtained 14 days after irradiation, and to a lesser extent at 30 days post-irradiation, the ability to form secondary organoids recovered to control levels. In contrast, cells obtained from glands at 90, 180, and 360 days post-irradiation irreversibly lost their ability to form organoids, indicating a time-dependent loss of regenerative potential. Transcriptomic analysis showed overexpression of Bmp4 in day 90 organoids derived from irradiated glands compared to the ones from day 14. Inhibition of Bmp4 using Noggin reversed this adverse response suggesting an important role in modulating SGSC function. Thus, early after irradiation, the regenerative potential of surviving SGSCs is preserved and comparable to that of unirradiated cells. At later time points after irradiation, SGSCs lose their regenerative potential suggesting that the prolonged exposure to a deleterious microenvironment leads to an irreversible decline in stemness. Modulation of Bmp4 signaling pathway might improve the regenerative potential of surviving SGSCs and enhance the efficiency of stem cell therapy in restoring the functionality of irradiated salivary glands.

			Action	DRS
	PG_SCP.7z	Other
	PG_Set02.zip	Other
	Result.7z	Other
	SMG_SCP.7z	Other
	SMG_Set02.zip	Other