Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
 DetailsÜbersicht
  Inactivation of Lsd1 triggers senscence in trophoblast stem cells by induction of Sirt4

Castex, J., Willmann, D., Kanouni, T., Arrigoni, L., Li, Y., Friedrich, M., et al. (2017). Inactivation of Lsd1 triggers senscence in trophoblast stem cells by induction of Sirt4. Cell Death and Disease, e2631-e2361. doi:10.1038/cddis.2017.48.

Item is

 

einblenden: alle ausblenden: alle

Basisdaten

einblenden: ausblenden:
Datensatz-Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-8572-7 Versions-Permalink: https://hdl.handle.net/21.11116/0000-0001-5CBD-4
Genre: Zeitschriftenartikel

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Castex, Josefina1, Autor
Willmann, Dominica1, Autor
Kanouni, Toufike1, Autor
Arrigoni, Laura2, Autor
Li, Yan1, Autor
Friedrich, Marcel1, Autor
Schleicher, Michael1, Autor
Wöhrle, Simon1, Autor
Pearson, Mark1, Autor
Kraut, Norbert1, Autor
Méret, Michaël1, Autor
Manke, Thomas2, Autor
Metzger, Eric1, Autor
Schüle, Roland1, Autor
Günther, Thomas1, Autor
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

Inhalt

einblenden:
ausblenden:
Schlagwörter: -
 Zusammenfassung: Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (Lsd1) triggers senescence in trophoblast stem cells (TSCs). Genome-wide transcriptional profiling of TSCs following Lsd1 inhibition shows gene set enrichment of aging and metabolic pathways. Consistently, global metabolomic and phenotypic analyses disclose an unbalanced redox status, decreased glutamine anaplerosis and mitochondrial function. Loss of homeostasis is caused by increased expression of sirtuin 4 (Sirt4), a Lsd1-repressed direct target gene. Accordingly, Sirt4 overexpression in wild-type TSCs recapitulates the senescence phenotype initiated by Lsd1 deletion or inhibition. Inversely, absence of Lsd1 enzymatic activity concomitant with knockdown of Sirt4 reestablishes normal glutamine anaplerosis, redox balance and mitochondrial function. In conclusion, by repression of Sirt4, Lsd1 directs the epigenetic control of TSC immortality via maintenance of metabolic flexibility.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 20172017
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1038/cddis.2017.48
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Cell Death and Disease
  Kurztitel : Cell Death Dis
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: London : Nature Publishing Group
Seiten: - Band / Heft: - Artikelnummer: - Start- / Endseite: e2631 - e2361 Identifikator: Anderer: 2041-4889
CoNE: https://pure.mpg.de/cone/journals/resource/20414889