Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells.
| Title: | Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells. |
|---|---|
| Authors: | Brunsdon, Hannah1,2, Brombin, Alessandro1,2, Peterson, Samuel3, Postlethwait, John H.3, Elizabeth Patton, E.1,2 e.patton@ed.ac.uk |
| Source: | Development (09501991). May2022, Vol. 149 Issue 10, p1-14. 14p. |
| Subject Terms: | *STEM cells, *ALDEHYDE dehydrogenase, *CELL physiology, *NEURAL crest, *GATEKEEPERS |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Development (09501991) is the property of Company of Biologists Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Academic Search Complete |
| FullText | Links: – Type: other Text: Availability: 0 CustomLinks: – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:a9h&genre=article&issn=09501991&ISBN=&volume=149&issue=10&date=20220515&spage=1&pages=1-14&title=Development (09501991)&atitle=Aldh2%20is%20a%20lineage-specific%20metabolic%20gatekeeper%20in%20melanocyte%20stem%20cells.&aulast=Brunsdon%2C%20Hannah&id=DOI:10.1242/dev.200277 Name: Full Text Finder (for New FTF UI) (s8985755) Category: fullText Text: Find It @ SCU Libraries MouseOverText: Find It @ SCU Libraries |
|---|---|
| Header | DbId: a9h DbLabel: Academic Search Complete An: 157364770 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Brunsdon%2C+Hannah%22">Brunsdon, Hannah</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Brombin%2C+Alessandro%22">Brombin, Alessandro</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Peterson%2C+Samuel%22">Peterson, Samuel</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Postlethwait%2C+John+H%2E%22">Postlethwait, John H.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Elizabeth+Patton%2C+E%2E%22">Elizabeth Patton, E.</searchLink><relatesTo>1,2</relatesTo><i> e.patton@ed.ac.uk</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Development+%2809501991%29%22">Development (09501991)</searchLink>. May2022, Vol. 149 Issue 10, p1-14. 14p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22STEM+cells%22">STEM cells</searchLink><br />*<searchLink fieldCode="DE" term="%22ALDEHYDE+dehydrogenase%22">ALDEHYDE dehydrogenase</searchLink><br />*<searchLink fieldCode="DE" term="%22CELL+physiology%22">CELL physiology</searchLink><br />*<searchLink fieldCode="DE" term="%22NEURAL+crest%22">NEURAL crest</searchLink><br />*<searchLink fieldCode="DE" term="%22GATEKEEPERS%22">GATEKEEPERS</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Development (09501991) is the property of Company of Biologists Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=a9h&AN=157364770 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1242/dev.200277 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 1 Subjects: – SubjectFull: STEM cells Type: general – SubjectFull: ALDEHYDE dehydrogenase Type: general – SubjectFull: CELL physiology Type: general – SubjectFull: NEURAL crest Type: general – SubjectFull: GATEKEEPERS Type: general Titles: – TitleFull: Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Brunsdon, Hannah – PersonEntity: Name: NameFull: Brombin, Alessandro – PersonEntity: Name: NameFull: Peterson, Samuel – PersonEntity: Name: NameFull: Postlethwait, John H. – PersonEntity: Name: NameFull: Elizabeth Patton, E. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 05 Text: May2022 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 09501991 Numbering: – Type: volume Value: 149 – Type: issue Value: 10 Titles: – TitleFull: Development (09501991) Type: main |
| ResultId | 1 |