Intrinsic mitotic activity supports the human salivary gland acinar cell population

Abstract

To develop treatments for salivary gland dysfunction, it is important to understand how human salivary glands are maintained under normal homeostasis. Previous data from our lab demonstrated that murine salivary acinar cells maintain the acinar cell population through self‐duplication under conditions of homeostasis, as well as after injury. Early studies suggested that human acinar cells are mitotically active, but the identity of the resultant daughter cells was not clear. Using markers of cell cycle activity and mitosis, as well as an ex vivo 5‐Ethynyl‐2´‐deoxyuridine assay, we show that human salivary gland acinar cells divide to generate daughter acinar cells. As in mouse, our data indicate that human salivary gland homeostasis is supported by the intrinsic mitotic capacity of acinar cells.

Cardiac cellular diversity and functionality in cardiac repair by single-cell transcriptomics

“…They divided cardiomyocytes into two groups, including less mature type or developing type (dCMs) with immature cardiomyocyte markers such as Myocd (also known as myocardin) and more mature type (mCMs) with abundant mitochondria and positive for muscle fiber markers such as Actc1 (also known as cardiac α-actin) ( Table 1 ) ( 14 ). Interestingly, some mCMs, such as those in the mCM1, also expressed these fibroblast-enriched markers (e.g., Col1a2, Col3a1, and Dcn), and Gata4 + or Myocd + nuclei were significantly enriched only in dCMs but not in mCMs or nonmyocyte cells.Partially different from the widely established markers of cardiomyocyte proliferation such as nucleotides analogs (EdU, BrdU), M-phase markers AURKB (Aurora B kinase) and pHH3 (phospho-histone H3), this study also entified a small population of presumably proliferating cardiomyocytes (pCMs) that expressed cell cycle genes (e.g., Mki67, Cenpp, and Kif15) ( Table 1 ), and found both P6 and P10 pCMs populations have the same similar gene signatures of cell proliferation: mitosis, G2/M transition, chromosome segregation and cytokinesis ( 14 – 16 ). A similar study explored whether a unique subset of preexisting cardiomyocytes could be regenerated by applying snRNA-seq (single-nucleus RNA sequencing) in healthy, injured and regenerating mice hearts ( 17 ) ( Table 2 ).…”

β-Adrenergic signaling induces Notch-mediated salivary gland progenitor cell control

“…The parotid SGs of patients taking β-blockers also still contain acinar cells, even in the face of reduced luminal ID progenitor cell activity. Perhaps, in an effort to compensate for both suppression of acinar cell activity induced via β-blocker use and β-blocker-induced luminal ID progenitor cell inactivity, acinar compartment-based progenitors proliferate to maintain acinar cell number ( Aure et al., 2015 ; Ingalls et al., 2019 ). Following a similar train of thought, we also acknowledge that only 1% of patients taking β-blockers will experience persistent hyposalivation under β-blocker administration.…”

Short-term and bystander effects of radiation on murine submandibular glands

“…Imaging and analysis were performed as previously described (Weng et al, 2018; Ingalls et al, 2020). Images for H&E staining were acquired using an Olympus DX41 microscope with a DP41 camera and analyzed using ImageJ software (National Institutes of Health, USA).…”