![]() By manipulating V m using a suite of tools, we establish a bioelectric pathway that regulates pluripotency in vertebrates, including human embryonic stem cells.Īction potentials are fundamental to the function of excitable cells, including neurons, cardiomyocytes, and pancreatic cells. ![]() Using high-resolution temporal transcriptome analysis, we identify the gene regulatory networks downstream of membrane depolarization and calcium signaling and discover that inhibition of the mTOR pathway transitions the pluripotent cell to a differentiated fate. In pluripotent embryonic cells, depletion of kcnh6 leads to membrane depolarization, elevation of intracellular calcium levels, and the maintenance of a pluripotent state at the expense of differentiation into ectodermal and myogenic lineages. By examining candidate genes of congenital heart disease and heterotaxy, we identify KCNH6, a member of the ether-a-go-go class of potassium channels that hyperpolarizes the V m and thus limits the activation of voltage gated calcium channels, lowering intracellular calcium. Here, we show that membrane voltage (V m) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. ![]() Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |