{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:51Z","timestamp":1790315991782,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tissue aging involves complex changes in vascular, immune, and stromal compartments that collectively reshape the local tissue ecosystem and may contribute to age-related diseases, including cancer, fibrotic diseases, and cardiovascular disease. However, it remains unclear whether reproducible, cell-specific vascular niche states emerge during aging and whether these states can be therapeutically targeted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A machine-learning single-cell age-clock model was constructed using three published human skin single-cell transcriptomic datasets and validated against chronological age. Vascular subpopulations were resolved by NMF clustering and diffusion pseudotime analysis. These findings were further validated in 15 human skin samples using H&amp;amp;E-based digital image analysis and immunohistochemistry. An inflammatory HMEC-1 model was used for RT-qPCR, flow cytometry, SA-\u03b2-gal staining, siRNA knockdown, and ChIP-qPCR. Structure-based virtual screening of an FDA drug library, molecular dynamics simulation, and biolayer interferometry were used to identify and validate ETS1-targeting compounds. Efficacy was assessed\n                      <jats:italic>in vivo<\/jats:italic>\n                      in a D-galactose-induced aging model treated with oral ipragliflozin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Predicted age correlated with chronological age, with vascular endothelial cells, lymphatic endothelial cells, and pericytes carrying the strongest aging signals. Aged skin showed a higher low-hematoxylin-area burden, reduced boundary-complexity variation, and reduced vascular-area heterogeneity. An aging-associated pericyte subcluster marked by MYO1B was identified, together with a continuous endothelial-to-pericyte transition (EndoPT). TGF-\u03b21\/IL-1\u03b2 stimulation induced MYO1B- and PDGFRB-positive pericyte-like transition and senescence in HMEC-1 cells. ETS1 bound the MYO1B promoter and was associated with aging status. Ipragliflozin bound the transcription-regulatory region of ETS1, suppressed the ETS1\u2013MYO1B axis, reduced EndoPT and senescence\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and restored epidermal thickness while reducing MYO1B, PDGFRB, and PAI-1 in aged rat skin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Multimodal profiling identifies an aging-associated ETS1-MYO1B vascular niche characterized by heightened inflammation, endothelial-to-pericyte plasticity, and cellular senescence, and demonstrates that this niche can be therapeutically targeted with ipragliflozin. As these processes also contribute to the microenvironmental remodeling observed in cancer and other age-related diseases, this niche may provide broader insight into how vascular and stromal alterations shape tissue aging and disease susceptibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1968248","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:40Z","timestamp":1790314300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal profiling uncovers an aging-associated ETS1-MYO1B vascular niche responsive to ipragliflozin"],"prefix":"10.3389","volume":"14","author":[{"given":"Mingzhu","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Shengjing Hospital, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haien","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shengjing Hospital, China Medical University","place":["Shenyang, China"]},{"name":"Department of Dermatology, The Seventh People's Hospital of Shenyang","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"You","sequence":"additional","affiliation":[{"name":"Department of Nursing, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nursing, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shengjing Hospital, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shengjing Hospital, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.devcel.2011.07.001","article-title":"Pericytes: developmental, physiological, and pathological perspectives, problems, and promises","volume":"21","author":"Armulik","year":"2011","journal-title":"Dev. 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