{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:09:04Z","timestamp":1788804544250,"version":"build-2803163510"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL145302"],"award-info":[{"award-number":["R01HL145302"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK136989"],"award-info":[{"award-number":["R01DK136989"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD094778"],"award-info":[{"award-number":["R01HD094778"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01EY027405"],"award-info":[{"award-number":["R01EY027405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35 HL166661-01"],"award-info":[{"award-number":["R35 HL166661-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    Airway structural remodeling and hyperresponsiveness (AHR), hallmarks of asthma, are influenced by genetic variations and adverse exposures. While intrauterine perturbations in lung development have been linked to adult pulmonary disease, the developmental origins of these abnormalities remain poorly understood. Here, we provide evidence of genetic background playing a key role in this process. Using A\/J and C57BL\/6J mice known for their distinct susceptibility to AHR, we show that A\/J embryos selectively develop an aberrant airway smooth muscle (SM) program and AHR in adulthood when exposed transiently to a vitamin A\/retinoic acid (RA)\u2013disrupted intrauterine environment in vivo by maternal BMS493 administration. Single-nucleus multiomics identified a mesenchymal cell population overactivating TGF-\u03b2 targets in response to BMS493 selectively in A\/J lungs. These cells, localized to sites of airway SM initiation and p-SMAD2- and -3, exhibited robust BMS493-mediated upregulation of SMAD2\/3 targets, including regulators of SM program\n                    <jats:italic>Pdgfra<\/jats:italic>\n                    and\n                    <jats:italic>Tnc<\/jats:italic>\n                    . Functional analyses in vivo and cultured lungs showed aberrant SM formation in areas of overactive TGF-\u03b2 of BMS493-exposed lungs. These abnormalities were prevented by inhibiting TGF-\u03b2 signaling in utero in RA-deficient embryos. These findings underscore how distinct genetic backgrounds respond to intrauterine perturbations that program airway structure and function, with potential lasting consequences in postnatal pulmonary function.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.200486","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:00:36Z","timestamp":1784649636000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic background influences developmental airway smooth muscle program and susceptibility to airway hyperresponsiveness in mice"],"prefix":"10.1172","volume":"11","author":[{"given":"Takehiro","family":"Otoshi","sequence":"first","affiliation":[{"name":"Columbia Center for Human Development, Department of Medicine, Division of Pulmonary Allergy and Critical Care Medicine, and Department of Genetics and Development, Columbia University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin 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