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Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila

Title
Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila
Type
Article in International Scientific Journal
Year
2018
Authors
Resende, LP
(Author)
Other
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Monteiro, A
(Author)
Other
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Bras, R
(Author)
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Lopes, T
(Author)
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Sunkel, CE
(Author)
ICBAS
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Journal
Vol. 217
Pages: 3930-3946
ISSN: 0021-9525
Other information
Authenticus ID: P-00P-VZZ
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.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 17
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