ArticleDevelopment (Cambridge, England)2022
Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Loss of MITF activity leads to emergent cell states from the melanocyte stem cell lineage.bioRxiv : the preprint server for biology · 2026Article
- The Regulatory Role ofAntioxidants (Basel, Switzerland) · 2025Article
- SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage.The Journal of investigative dermatology · 2025Article
- Arsenic disrupts H3K9me3 and H3K27me3 balance by biasing PRC2.1 and PRC2.2 activity via PALI1 inhibition in carcinogenesis.International journal of biological sciences · 2025Article
- Distinct DNA repair mechanisms prevent formaldehyde toxicity during development, reproduction and aging.Nucleic acids research · 2024Article
- Melanocyte lineage dynamics in development, growth and disease.Development (Cambridge, England) · 2024Review
- ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.Cell reports · 2024Article
- Variant Allele ofVaccines · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
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 - the one-carbon (1C) building block for nucleotide biosynthesis - 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.