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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:p>\n                    Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and its regulation are important for endothelial cell (EC) function and signaling. Yet, the spatiotemporal organization of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity and its regulation across a vascular plexus is poorly understood in an in vivo mammalian context. To overcome this gap in knowledge, we developed an intravital imaging approach to resolve Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity with single-cell resolution in skin vasculature of adult mice via multiphoton microscopy. Here, we tracked thousands of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    events in the skin capillary plexus during homeostasis and observed signaling heterogeneity between ECs, with just over half displaying Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity at any given time. Longitudinal tracking of the same mice revealed that the same capillary ECs maintain Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity over days to weeks. Interestingly, activity dynamics, such as frequency and event duration, are not conserved at a single-cell level but are maintained at an EC population level. Molecularly, conditional deletion of the gap junction protein Connexin 43 (Cx43cKO) in ECs leads to a subset of ECs displaying sustained Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity, biasing signaling dynamics of the whole network toward chronically persistent activity over time. Sustained capillary Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity results in vascular permeability and flow dysregulation. Last, through pharmacological targeting of known agonists\/antagonists, we showed that inhibition of L-type Voltage Gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels non-cell-autonomously restores Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity, blood flow, and barrier function in Cx43cKO mice. Collectively, our work provides insight into the spatial and temporal characteristics, extent, and regulation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activity in skin capillaries of live mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519708123","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T18:06:47Z","timestamp":1782238007000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Skin capillary endothelial cells form a network of spatiotemporally conserved Ca\n                    <sup>2+<\/sup>\n                    activity"],"prefix":"10.1073","volume":"123","author":[{"given":"Anush","family":"Swaminathan","sequence":"first","affiliation":[{"name":"Department of Genetics, Yale School of Medicine","place":["New 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Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7577-7127","authenticated-orcid":false,"given":"Jessica L.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-0091","authenticated-orcid":false,"given":"Zhongqi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ushnish","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine","place":["New 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Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-2129","authenticated-orcid":false,"given":"Chen Yuan","family":"Kam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Dermatology, Department of Medicine, University of California","place":["Los Angeles"]},{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Broad Stem Cell Research Center, University of California","place":["Los Angeles"]},{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular, Cell and Developmental Biology, University of California","place":["Los 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