{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:42:08Z","timestamp":1792212128426,"version":"4.4.0"},"reference-count":81,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 OD011116"],"award-info":[{"award-number":["R01 OD011116"]}],"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":["R24 OD018555"],"award-info":[{"award-number":["R24 OD018555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Research Council","award":["ZF-MEL-CHEMBIO-648489"],"award-info":[{"award-number":["ZF-MEL-CHEMBIO-648489"]}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"crossref","award":["687306"],"award-info":[{"award-number":["687306"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The University of Edinburgh MRC Human Genetics Unit","award":["MC_UU_00007\/9"],"award-info":[{"award-number":["MC_UU_00007\/9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Melanocyte stem cells (McSCs) in zebrafish serve as an on-demand source of melanocytes during growth and regeneration, but metabolic programs associated with their activation and regenerative processes are not well known. Here, using live imaging coupled with scRNA-sequencing, we discovered that, during regeneration, quiescent McSCs activate a dormant embryonic neural crest transcriptional program followed by an aldehyde dehydrogenase (Aldh) 2 metabolic switch to generate progeny. Unexpectedly, although ALDH2 is well known for its aldehyde-clearing mechanisms, we find that, in regenerating McSCs, Aldh2 activity is required to generate formate \u2013 the one-carbon (1C) building block for nucleotide biosynthesis \u2013 through formaldehyde metabolism. Consequently, we find that disrupting the 1C cycle with low doses of methotrexate causes melanocyte regeneration defects. In the absence of Aldh2, we find that purines are the metabolic end product sufficient for activated McSCs to generate progeny. Together, our work reveals McSCs undergo a two-step cell state transition during regeneration, and that the reaction products of Aldh2 enzymes have tissue-specific stem cell functions that meet metabolic demands in regeneration.<\/jats:p>","DOI":"10.1242\/dev.200277","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T06:22:39Z","timestamp":1651213359000},"source":"Crossref","is-referenced-by-count":14,"title":["Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells"],"prefix":"10.1242","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-6500","authenticated-orcid":false,"given":"Hannah","family":"Brunsdon","sequence":"first","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"},{"name":"Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-9248","authenticated-orcid":false,"given":"Alessandro","family":"Brombin","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"},{"name":"Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Peterson","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Postlethwait","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-0834","authenticated-orcid":false,"given":"E. Elizabeth","family":"Patton","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"},{"name":"Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"2022051915500403100_DEV200277C1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.cell.2009.07.049","article-title":"Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin","volume":"139","author":"Adameyko","year":"2009","journal-title":"Cell"},{"key":"2022051915500403100_DEV200277C2","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3945\/jn.116.244467","article-title":"Alcohol dehydrogenase 5 is a source of formate for de novo purine biosynthesis in HepG2 cells","volume":"147","author":"Bae","year":"2017","journal-title":"J. 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