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  Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity

Schönberger, K., Obier, N., Romero-Mulero, M. C., Cauchy, P., Mess, J., Pavlovich, P. V., et al. (2022). Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity. Cell Stem Cell, 29, 131-148. doi:10.1016/j.stem.2021.10.002.

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Schoenberger et al. 2022.pdf (Publisher version), 8MB
 
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2021
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2021 Elsevier Inc.
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 Creators:
Schönberger, Katharina1, Author              
Obier, Nadine1, Author
Romero-Mulero, Mari Carmen1, Author
Cauchy, Pierre1, Author              
Mess, Julian1, Author
Pavlovich, Polina V.1, Author
Zhang, Yu Wei1, Author
Mitterer, Michael2, Author
Rettkowski, Jasmin1, Author
Lalioti, Maria-Eleni1, Author
Jäcklein, Karin1, Author
Curtis, Jonathan D.3, Author
Féret, Betty4, Author
Sommerkamp, Pia4, Author
Morganti, Claudia4, Author
Ito, Keisuke4, Author
Ghyselinck, Norbert B.4, Author
Trompouki, Eirini1, Author              
Büscher, Jörg Martin2, Author              
Pearce, Erika Laine3, Author              
Cabezas-Wallscheid, Nina1, Author               more..
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              
3Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              
4External Organizations, ou_persistent22              

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 Abstract: Hematopoietic stem cells (HSCs) rely on complex regulatory networks to preserve stemness. Due to the scarcity of HSCs, technical challenges have limited our insights into the interplay between metabolites, transcription, and the epigenome. In this study, we generated low-input metabolomics, transcriptomics, chromatin accessibility, and chromatin immunoprecipitation data, revealing distinctmetabolic hubs that are enriched in HSCs and their downstream multipotent progenitors. Mechanistically, we uncover a non-classical retinoic acid (RA) signaling axis that regulates HSC function. We show that HSCs rely on Cyp26b1, an enzyme conventionally considered to limit RA effects in the cell. In contrast to the traditional view, we demonstrate that Cyp26b1 is indispensable for production of the active metabolite 4-oxo-RA. Further, RA receptor beta (Rarb) is required for complete transmission of 4-oxo-RA-mediated signaling to maintain stem cells. Our findings emphasize that a single metabolite controls stem cell fate by instructing epigenetic and transcriptional attributes.

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Language(s): eng - English
 Dates: 2021-10-262022-01-06
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.stem.2021.10.002
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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 29 Sequence Number: - Start / End Page: 131 - 148 Identifier: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909