{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:55:58Z","timestamp":1791518158263,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"36","license":[{"start":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T00:00:00Z","timestamp":1693267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003384"],"award-info":[{"award-number":["82003384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR060306 and GM125322"],"award-info":[{"award-number":["AR060306 and GM125322"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:p>Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility\u2013increasing events before calming down. The self-organizing processes are controlled by a morphogenetic module composed of molecular sensors, modulators, and executers. Increasing dermal stiffness provides the initial driving force (driver) which activates Yap1 (sensor) in epidermal cysts. Notch signaling (modulator 1) in epidermal cyst tunes the threshold of Yap1 activation. Activated Yap1 induces Wnts and MMPs (epidermal executers) in basal cells to facilitate cellular flows, allowing epidermal cells to protrude out from the CMU. Dermal cell\u2013expressed Rock (dermal executer) generates a stiff force bridge between two CMU and accelerates tissue mixing via activating Laminin and \u03b21-integrin. Thus, this self-organizing coalescence process is controlled by a mechano-chemical circuit. Beyond skin, self-organization in organoids may use similar mechano-chemical circuit structures.<\/jats:p>","DOI":"10.1073\/pnas.2221982120","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T13:38:35Z","timestamp":1693316315000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["The mechano-chemical circuit drives skin organoid self-organization"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4271-2714","authenticated-orcid":false,"given":"Mingxing","family":"Lei","sequence":"first","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology of Ministry of Education &amp; 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China"},{"name":"Integrative Stem Cell Center, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-5614","authenticated-orcid":false,"given":"Hans I-Chen","family":"Harn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science &amp; 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