Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Resende, LP (Autor) Outra; Monteiro, A (Autor) Outra; Bras, R (Autor) Outra; Lopes, T (Autor) Outra; Sunkel, CE (Autor) ICBAS

Revista

Título: Journal of Cell Biology

Vol. 217

Páginas: 3930-3946

ISSN: 0021-9525

Editora: Rockefeller University Press

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 8 Citações

Outras Informações

ID Authenticus: P-00P-VZZ

DOI: 10.1083/jcb.201804205

Abstract (EN): Aneuploidy is associated with different human diseases including cancer. However, different cell types appear to respond differently to aneuploidy, either by promoting tumorigenesis or causing cell death. We set out to study the behavior of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of chromosome missegregation either by abrogation of the spindle assembly checkpoint or through kinetochore disruption or centrosome amplification. These conditions induce moderate levels of aneuploidy in ISCs, and we find no evidence of apoptosis. Instead, we observe a significant accumulation of ISCs associated with increased stem cell proliferation and an excess of enteroendocrine cells. Moreover, aneuploidy causes up-regulation of the JNK pathway throughout the posterior midgut, and specific inhibition of JNK signaling in ISCs is sufficient to prevent dysplasia. Our findings highlight the importance of understanding the behavior of different stem cell populations to aneuploidy and how these can act as reservoirs for genomic alterations that can lead to tissue pathologies.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17