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

Abstract 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 sali...

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Main Authors: Syed Mohammed Musheer Aalam, Ana Rita Varela, Aalim Khaderi, Ronsard J. Mondesir, Dong-Gi Mun, Andrew Ding, Isabelle M. A. Lombaert, Rob P. Coppes, Chitra Priya Emperumal, Akhilesh Pandey, Jeffrey R. Janus, Nagarajan Kannan
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-025-00410-5
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author Syed Mohammed Musheer Aalam
Ana Rita Varela
Aalim Khaderi
Ronsard J. Mondesir
Dong-Gi Mun
Andrew Ding
Isabelle M. A. Lombaert
Rob P. Coppes
Chitra Priya Emperumal
Akhilesh Pandey
Jeffrey R. Janus
Nagarajan Kannan
author_facet Syed Mohammed Musheer Aalam
Ana Rita Varela
Aalim Khaderi
Ronsard J. Mondesir
Dong-Gi Mun
Andrew Ding
Isabelle M. A. Lombaert
Rob P. Coppes
Chitra Priya Emperumal
Akhilesh Pandey
Jeffrey R. Janus
Nagarajan Kannan
author_sort Syed Mohammed Musheer Aalam
collection DOAJ
description Abstract 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 PSMA- phenotypes of both submandibular and parotid glands, with clonal differentiation assays highlighting heterogeneity. Induction of PSMA/FOLH1 expression was associated with SGSPC differentiation. Using mass spectrometry-based single cell proteomics, we identified 2461 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 provide a foundation for SGSPC research and potential regenerative therapies for salivary gland dysfunction.
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spelling doaj-art-a68964e01c5d4a299eabcad0da2ac23c2025-08-20T01:52:25ZengNature Portfolionpj Regenerative Medicine2057-39952025-05-0110111910.1038/s41536-025-00410-5Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1Syed Mohammed Musheer Aalam0Ana Rita Varela1Aalim Khaderi2Ronsard J. Mondesir3Dong-Gi Mun4Andrew Ding5Isabelle M. A. Lombaert6Rob P. Coppes7Chitra Priya Emperumal8Akhilesh Pandey9Jeffrey R. Janus10Nagarajan Kannan11Department of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicBiologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, 1011 N. University AveDepartments of Radiation Oncology and Biomedical Sciences, University of Groningen, University Medical Center GroningenDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Otolaryngology-Head and Neck Surgery, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicAbstract 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 PSMA- phenotypes of both submandibular and parotid glands, with clonal differentiation assays highlighting heterogeneity. Induction of PSMA/FOLH1 expression was associated with SGSPC differentiation. Using mass spectrometry-based single cell proteomics, we identified 2461 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 provide a foundation for SGSPC research and potential regenerative therapies for salivary gland dysfunction.https://doi.org/10.1038/s41536-025-00410-5
spellingShingle Syed Mohammed Musheer Aalam
Ana Rita Varela
Aalim Khaderi
Ronsard J. Mondesir
Dong-Gi Mun
Andrew Ding
Isabelle M. A. Lombaert
Rob P. Coppes
Chitra Priya Emperumal
Akhilesh Pandey
Jeffrey R. Janus
Nagarajan Kannan
Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
npj Regenerative Medicine
title Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
title_full Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
title_fullStr Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
title_full_unstemmed Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
title_short Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1
title_sort establishment of salivary tissue organoid biorepository characterizing salivary gland stem progenitor cells and novel differentiation marker psma folh1
url https://doi.org/10.1038/s41536-025-00410-5
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