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  Differential Alternative Polyadenylation Landscapes Mediate Hematopoietic Stem Cell Activation and Regulate Glutamine Metabolism

Sommerkamp, P., Altamura, S., Renders, S., Narr, A., Ladel, L., Zeisberger, P., et al. (2020). Differential Alternative Polyadenylation Landscapes Mediate Hematopoietic Stem Cell Activation and Regulate Glutamine Metabolism. Cell Stem Cell, 26, 722-738. doi:10.1016/j.stem.2020.03.003.

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Sommerkamp et al..pdf (Verlagsversion), 3MB
 
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 Urheber:
Sommerkamp, Pia1, Autor
Altamura, Sandro1, Autor
Renders, Simon1, Autor
Narr, Andreas1, Autor
Ladel, Luisa1, Autor
Zeisberger, Petra1, Autor
Eiben, Paula Leonie1, Autor
Fawaz, Malak1, Autor
Rieger, Michael A.1, Autor
Cabezas-Wallscheid, Nina2, Autor           
Trumpp, Andreas1, Autor
Affiliations:
1External Organizations, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, ou_2243641              

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Schlagwörter: alternative polyadenylation; APAome; 3′-seq; hematopoietic stem cell; inflammation; glutaminolysis; Pabpn1; Nudt21; GAC; KGA
 Zusammenfassung: Alternative polyadenylation (APA) is emerging as an important regulatory mechanism of RNA and protein isoform expression by controlling 3′ untranslated region (3′-UTR) composition. The relevance of APA in stem cell hierarchies remains elusive. Here, we first demonstrate the requirement of the APA regulator Pabpn1 for hematopoietic stem cell (HSC) function. We then determine the genome-wide APA landscape (APAome) of HSCs and progenitors by performing low-input 3′ sequencing paired with bioinformatic pipelines. This reveals transcriptome-wide dynamic APA patterns and an overall shortening of 3′-UTRs during differentiation and upon homeostatic or stress-induced transition from quiescence to proliferation. Specifically, we show that APA regulates activation-induced Glutaminase (Gls) isoform switching by Nudt21. This adaptation of the glutamine metabolism by increasing the GAC:KGA isoform ratio fuels versatile metabolic pathways necessary for HSC self-renewal and proper stress response. Our study establishes APA as a critical regulatory layer orchestrating HSC self-renewal, behavior, and commitment.

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Sprache(n): eng - English
 Datum: 2020-03-30
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.stem.2020.03.003
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Titel: Cell Stem Cell
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Cambridge, Mass. : Cell Press
Seiten: - Band / Heft: 26 Artikelnummer: - Start- / Endseite: 722 - 738 Identifikator: ISSN: 1934-5909
CoNE: https://pure.mpg.de/cone/journals/resource/1934-5909