Calcium signaling in human pluripotent stem cells

Abstract

a b s t r a c tHuman pluripotent stem cells provide new tools for developmental and pharmacological studies as well as for regenerative medicine applications. Calcium homeostasis and ligand-dependent calcium signaling are key components of major cellular responses, including cell proliferation, differentiation or apoptosis. Interestingly, these phenomena have not been characterized in detail as yet in pluripotent human cell sates. Here we review the methods applicable for studying both short-and long-term calcium responses, focusing on the expression of fluorescent calcium indicator proteins and imaging methods as applied in pluripotent human stem cells. We discuss the potential regulatory pathways involving calcium responses in hPS cells and compare these to the implicated pathways in mouse PS cells. A recent development in the stem cell field is the recognition of so called "naïve" states, resembling the earliest potential forms of stem cells during development, as well as the "fuzzy" stem cells, which may be alternative forms of pluripotent cell types, therefore we also discuss the potential role of calcium homeostasis in these PS cell types.

Characterization of calcium signals in human induced pluripotent stem cell-derived dentate gyrus neuronal progenitors and mature neurons, stably expressing an advanced calcium indicator protein

“…For in vitro calcium measurement calcium sensitive dyes, such as Fluo-4/AM, Fura-2/AM or Oregon green 488 BAPTA-1 AM (OGB1-AM), are extensively used, while for in vivo experiments the use of genetically engineered calcium indicator (GECI) proteins is greatly increasing (Rose, T. et al, 2014;Apati, A. et al, 2016;Dana, H. et al, 2016). In our previous study (Apati, A. et al, 2013), we compared the application of the calcium sensitive fluorescent dye, Fluo-4, and the GECI GCaMP2, for studying calcium signaling in human PSCs.…”

Mitochondria and the dynamic control of stem cell homeostasis

“…The regulation of intracellular calcium might be crucial for the physiological differentiation of PSCs and adult stem cells, including MSCs and NSCs . Nonetheless, the specific importance of mitochondrial calcium regulation for stem cell homeostasis remains overall under‐investigated .…”

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“…Its extracellular level is highly important for various physiological activities such as cellular responses and cell signaling. Calcium homeostasis and ligand-dependent calcium signaling are key components of major cellular responses, including cell proliferation, differentiation or apoptosis [65] (Figure 7). Importantly, the bones contain 99% of the Ca ++ in the body, so bones provide a reservoir of Ca ++ that can be used to maintain [Ca ++ ] ECF .…”