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Review
. 2020 Jun 4;21(6):e50028.
doi: 10.15252/embr.202050028. Epub 2020 May 17.

Calcium regulation of stem cells

Hans-Willem Snoeck  1   2   3   4
Affiliations
Review

Calcium regulation of stem cells

Hans-Willem Snoeck. EMBO Rep. .

Abstract

Pluripotent and post-natal, tissue-specific stem cells share functional features such as the capacity to differentiate into multiple lineages and to self-renew, and are endowed with specific cell maintenance mechanism as well as transcriptional and epigenetic signatures that determine stem cell identity and distinguish them from their progeny. Calcium is a highly versatile and ubiquitous second messenger that regulates a wide variety of cellular functions. Specific roles of calcium in stem cell niches and stem cell maintenance mechanisms are only beginning to be explored, however. In this review, I discuss stem cell-specific regulation and roles of calcium, focusing on its potential involvement in the intertwined metabolic and epigenetic regulation of stem cells.

Keywords: calcium; epigenetics; metabolism; pluripotent stem cells; post-natal stem cells.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. Calcium regulation in cells
Schematic representation of cellular calcium influx, efflux, and buffering mechanisms. DAG: diacylglycerol; IP3: inositol 1,4,5‐triphosphate; MCU: mitochondrial calcium uniporter; NCLX: mitochondrial sodium/calcium exchanger; NCX: plasma membrane sodium/calcium exchanger; ORAI1: calcium release‐activated calcium channel protein 1; PIP2: phosphoinositol 4,5‐biphosphate; PLC: phospholipase C; PMCA: plasma membrane calcium efflux pump; SERCA: sarcoplasmatic calcium pump; RyR: ryanodine receptor; STIM1: stromal interaction molecule 1; VDAC1: voltage‐dependent anion‐selective channel 1.
Figure 2
Figure 2. Calcium regullation in various stem cell types and niches
Schematic representation of calcium concentration and its effect in HSCs (A), skin (B), in vitro cultured keratinocytes (C), mESCs (D), and fly ISCs (E).
Figure 3
Figure 3. Calcium regulation of DNA and histone modifications
Schematic representation of potential direct regulation of covalent histone and DNA modifications by calcium. 5hmC: 5 hydroxymethyl cytosine; 5mC: 5‐methyl cytosine; CaMKII: calcium/calmodulin‐dependent kinase 2; HDAC4: histone deacetylase 4; MeCP2: methyl CpG‐binding protein 2; TET: ten‐eleven translocated.
Figure 4
Figure 4. Calcium regulation of cellular metabolism and its repercussion on epigenetic modifications
Effect of calcium on mitochondrial function and on mitochondrial metabolites involved in chromatin remodeling. Enzymes activated by calcium are marked in red. DHA: dihydroxyacetone phosphate; ETC: electron transport chain; G3P: glycerol‐3‐phosphate; GPD2: glycerol‐3‐phosphate dehydrogenase 2; IDH: isocitrate dehydrogenase; KGD: α‐ketoglutarate dehydrogenase; OAA: oxaloacetic acid; PDH: pyruvate dehydrogenase complex; PDP1: pyruvate dehydrogenase phosphatase 1.
Figure 5
Figure 5. Interplay between calcium, glycolysis and TCA
Interplay between regulation of intracellular calcium by glycolysis and its effect on the TCA and chromatin remodeling. ETC: electron transport chain; OAA: oxaloacetic acid; PMCA: plasma membrane calcium efflux pump; TCA: tricarboxylic acid cycle.
See this image and copyright information in PMC

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