Differential activation of Ca2+ influx channels modulate stem cell potency, their proliferation/viability and tissue regeneration

Naseem Ahamad, Yuyang Sun, Viviane Nascimento Da Conceicao, Caroline R.D. Xavier Paul Ezhilan, Mohan Natarajan, Brij B. Singh

Research output: Contribution to journalArticlepeer-review

Abstract

Stem cells have indefinite self-renewable capability; however, factors that modulate their pluripotency/function are not fully identified. Here we show that store-dependent Ca2+ entry is essential for modulating the function of bone marrow-derived mesenchymal stem cells (MSCs). Increasing external Ca2+ modulated cell cycle progression that was critical for MSCs survival. Additionally, Ca2+ was critical for stem proliferation, its differentiation, and maintaining stem cell potential. Ca2+ channel characterization, including gene silencing, showed two distinct Ca2+ entry channels (through Orai1/TRPC1 or via Orai3) that differentially regulate the proliferation and viability of MSCs. Importantly, NFκB translocation, but not JNK/ERK into the nucleus, was observed upon store depletion, which was blocked by the addition of Ca2+ channel inhibitors. Radiation lead to a decrease in saliva secretion, decrease in acinar cell number, and enlarged ducts were observed, which were restored by the transplantation of stem cells that were propagated in higher Ca2+. Finally radiation showed a decrese in TRPC1 expression along with a decrese in AQP5, which was again restored upon MSC tranplantation. Together these results suggest that Ca2+ entry is essential for stem cell function that could be critical for regenerative medicine.

Original languageEnglish (US)
Article number67
Journalnpj Regenerative Medicine
Volume6
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Developmental Biology
  • Cell Biology

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