Role of quiescent cells in the homeostatic maintenance of the adult submandibular salivary gland

Paola Serrano Martinez; Martti Maimets; Reinier Bron; Ronald van Os; Gerald de Haan; Sarah Pringle; Robert P Coppes

doi:10.1016/j.isci.2022.105047

Role of quiescent cells in the homeostatic maintenance of the adult submandibular salivary gland

iScience. 2022 Sep 2;25(10):105047. doi: 10.1016/j.isci.2022.105047. eCollection 2022 Oct 21.

Authors

Paola Serrano Martinez^{1

2}, Martti Maimets^{1

2}, Reinier Bron^{1

2

3}, Ronald van Os⁴, Gerald de Haan⁴, Sarah Pringle⁵, Robert P Coppes^{1

2}

Affiliations

¹ Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
² Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands.
³ Department of Biomedical Engineering, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
⁴ Department of Biology of Aging, Section Stem Cell Biology, European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
⁵ Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.

Abstract

Stem/progenitor cells are required for maintenance of salivary gland (SG) function and serve as untapped reservoirs to create functional cells. Despite recent advancements in the identification of stem/progenitor pools, in the submandibular gland (SMG), a knowledge gap remains. Furthermore, the contribution to adult SMG homeostasis of stem/progenitor cells originating from embryonic development is unclear. Here, we employ an H2B-GFP embryonic and adult pulse-and-chase system to characterize potential SMG stem/progenitor cells (SGSCs) based on quiescence at different stages. Phenotypical profiling of quiescent cells in the SMG revealed that label-retaining cells (LRCs) of embryonic or adult origin co-localized with CK8+ ductal or vimentin + mesenchymal, but not with CK5+ or CK14 + stem/progenitor cells. These SMG LRCs failed to self-renew in vitro while non-label retaining cells displayed differentiation and long-term expansion potential as organoids. Collectively, our data suggest that an active cycling population of cells is responsible for SMG homeostasis with organoid forming potential.

Keywords: Biological sciences; Cell biology; Stem cells research.