Ca²⁺‐depended signaling pathways regulate self‐renewal and pluripotency of stem cells

Abstract

Ca -mediated signaling is widely spread in nature and plays critical role in the individual development of various organisms ranging from microorganisms to mammals. In vertebrates, Ca is involved in important developmental events: fertilization, body plan establishment, and organogenesis. The two later events are defined by embryonic stem cells (ESCs). ESCs are capable of self-renewal and are pluripotent by nature, that is, can give rise to all types of cells that make up the body. Given the paramount importance of Ca signalization in the development, it is therefore not surprising this process also plays role in the biology of stem cells. In this review, we scrutinize the published experimental data on the role of Ca ions in embryonic stem cells self-renewal and pluripotency. In line with this, we also discuss possible mechanisms of p53 inhibition as a major hindrance to self-renewal of ESCs. Finally, we argue about the role of G-protein-coupled receptors (GPCRs), the largest family of heteromeric transmembrane receptors, and GPCR-mediated signalization in stem cells, and propose the role for the GPCR-G-protein-PLC-Ca -downstream signaling pathway in the regulation of pluripotency of both mouse and human ESCs.

Characterization of intracellular buffering power in human induced pluripotent stem cells and the loss of pluripotency is delayed by acidic stimulation and increase of NHE1 activity

“…Moreover, activation of NHE1 increased the pH i on the side of lamellipodia more than on the other side, and this gradient collapsed upon the inhibition of NHE1 (Denker & Barber, 2002). Apart from the pH i regulation, NHE1 was also involved in various cellular functions, such as Ca 2+ (Apati, Berecz, & Sarkadi, 2016; Ermakov, Daks, Fedorova, Shuvalov, & Barlev, 2018; Lu et al, 2017; Richard D Vaughan‐Jones, Spitzer, & Swietach, 2009) and hypoxia‐adaption (Forristal, Wright, Hanley, Oreffo, & Houghton, 2010; S. K. Parks et al, 2013; Yoshida, Takahashi, Okita, Ichisaka, & Yamanaka, 2009), which were associated with the regulation of PSCs differentiation. Therefore, we consider that the active pH i regulators, such as NHE1, were necessary for dynamic homeostasis of pH i and further regulated the cellular functions.…”

Calcium Signaling in Vertebrate Development and Its Role in Disease

“…It is well known that developing embryos up to the blastocyst stage of development and embryonic stem cells exhibit the ability to either maintain stem cell identity or differentiate into the lineages of all three germ layers. This opens new avenues for the exploration of these cells’ potential uses in regenerative medicine [ 139 , 140 , 141 ]. The ultimate goal of regenerative medicine is to restore or substitute damaged tissue so the tissue can maintain its function(s); this may require boosting natural defense systems, which could harness and accelerate innate healing processes in order to cure previously unmanageable medical problems [ 142 ].…”

How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?

“…Cancer stem cells (CSCs) are a small subpopulation of cells within malignancy groups with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host [ 45 ]. Generally, they are resistant to chemotherapeutics, possess tumor-initiating and metastasis-initiating capacities, and are responsible for tumor recurrence and development [ 46 , 47 ].…”