| Online-Ressource |
Verfasst von: | Sommerkamp, Pia [VerfasserIn]  |
| Altamura, Sandro [VerfasserIn]  |
| Renders, Simon [VerfasserIn]  |
| Narr, Andreas [VerfasserIn]  |
| Ladel, Luisa [VerfasserIn]  |
| Zeisberger, Petra [VerfasserIn]  |
| Eiben, Paula Leonie [VerfasserIn]  |
| Fawaz, Malak [VerfasserIn]  |
| Rieger, Michael A. [VerfasserIn]  |
| Cabezas-Wallscheid, Nina [VerfasserIn]  |
| Trumpp, Andreas [VerfasserIn]  |
Titel: | Differential alternative polyadenylation landscapes mediate hematopoietic stem cell activation and regulate glutamine metabolism |
Verf.angabe: | Pia Sommerkamp, Sandro Altamura, Simon Renders, Andreas Narr, Luisa Ladel, Petra Zeisberger, Paula Leonie Eiben, Malak Fawaz, Michael A. Rieger, Nina Cabezas-Wallscheid, Andreas Trumpp |
E-Jahr: | 2020 |
Jahr: | March 30, 2020 |
Umfang: | 17 S. |
Fussnoten: | Gesehen am 06.04.2020 |
Titel Quelle: | Enthalten in: Cell stem cell |
Ort Quelle: | Amsterdam [u.a.] : Elsevier, 2007 |
Jahr Quelle: | 2020 |
Band/Heft Quelle: | 26(2020), 5, Seite 722-738.e7 |
ISSN Quelle: | 1875-9777 |
Abstract: | 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. |
DOI: | doi:10.1016/j.stem.2020.03.003 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.stem.2020.03.003 |
| Volltext: http://www.sciencedirect.com/science/article/pii/S1934590920300953 |
| DOI: https://doi.org/10.1016/j.stem.2020.03.003 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | 3′-seq |
| alternative polyadenylation |
| APAome |
| GAC |
| glutaminolysis |
| hematopoietic stem cell |
| inflammation |
| KGA |
K10plus-PPN: | 1694097943 |
Verknüpfungen: | → Zeitschrift |
Differential alternative polyadenylation landscapes mediate hematopoietic stem cell activation and regulate glutamine metabolism / Sommerkamp, Pia [VerfasserIn]; March 30, 2020 (Online-Ressource)