Wiley Interdiscip Rev Syst Biol Med - Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.


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Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behavior and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatiotemporal gradients of these endogenous transmembrane voltage potentials (Vmem ) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells' programs toward the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in nonneural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering.

Resumo Limpo

transform impact regen medicin requir reprogram individu cell advanc repair strategi birth defect injuri tumor normal construct bioengin organ tissu requir abil control largescal anatom shape much recent work focus transcript biochem regul cell behavior morphogenesi howev excit new data reveal bioelectr properti cell microenviron exert profound influenc cell differenti prolifer migrat ion channel pump express cell just excit nerv muscl establish rest potenti vari across tissu chang signific development event import spatiotempor gradient endogen transmembran voltag potenti vmem serv instruct pattern cue largescal anatomi provid organ ident posit inform prepattern templat cue morphogenesi new genet pharmacolog techniqu molecular modul bioelectr gradient vivo reveal abil initi complex organogenesi chang tissu ident trigger regener whole vertebr appendag larg segment spatial inform process orchestr individu cell program toward anatom need host organ electr blur line memori decisionmak neural network morphogenesi nonneur tissu advanc crack bioelectr code will enabl ration reprogram shape whole tissu organ revolution regen medicin development biolog synthet bioengin

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