Ion channels in stem cell differentiation

Wilson (1896) argued that egg cytoplasm is primarily totipotent, its regions standing in no fixed relation to the parts they give rise to.¹ He held that mosaic-like development arises secondarily, through local chemical and physical differentiation whose extent varies between eggs.¹ Morgan (1901) separated two ideas: that blastomeres are potentially equal because they are alike, and that they are totipotent despite differences. He preferred the second, citing sea-urchin blastomeres that each make a whole embryo.² Driesch (1908) recorded Bergson's remark that organic finality would be external, since the whole forms by self-limitation of totipotent parts, and said the difficulty disappears from his own categorical standpoint.³

Pillozzi and Becchetti (2012) described a progressive restriction of potency. Totipotent blastomeres give way to pluripotent cells, and then to slowly dividing adult stem cells that generate transit amplifying cells.⁴ They noted that it is uncertain whether the range of outcomes in neural stem cells reflects extrinsic regulation or heterogeneous stem cell populations.⁴ Rink (2013) reported that Wagner and colleagues rescued a lethally irradiated planarian by transplanting one neoblast, which he took as conclusive evidence of pluripotency.⁶ Totipotency was not formally shown, because the donors came from asexual animals.⁶

Simanov and colleagues (2012) compared transcriptomes of irradiated, stem cell-deficient flatworms with untreated animals. They found ion channel genes expressed specifically in dividing cells, and proposed these as candidates for studying bioelectric signalling in stem cell maintenance.⁵ Sundelacruz, Levin and Kaplan (2015) summarised work on induced pluripotent stem cells, which express many channel types and in which tetraethylammonium block of potassium channels inhibited proliferation and viability.⁸ In mouse embryonic stem cells, depolarization by Kv channel blockade reduced proliferation and pluripotency markers Oct-4, Sox-2 and Nanog, and raised early germ layer markers.⁸

Yang and Brackenbury (2013) noted that stem cells and cancer cells share the ability to differentiate and self-renew, increased membrane transporter activity and the ability to migrate and metastasize.⁷ O'Hara-Wright and colleagues (2022) called bioelectricity a lesser studied cue that has been shown to regulate central nervous system development and function.⁹ They discussed electrical stimulation as a way to engineer next-generation organoids from pluripotent stem cells, and observed that stem cell technology has not yet merged with this area of bioelectricity.⁹