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Title

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra
Authors
Tomczyk, Szymon
Suknovic, Nenad Slavko
Schenkelaars, Quentin
Wenger, Yvan
Ekundayo, Kazadi
Buzgariu, Wanda Christa
Bauer, Christoph Ruediger
Fischer, Kathleen
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Published in Development. 2020, vol. 147, no. dev177840, p. 1-16
Abstract Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris. However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within 3 months. This phenotype is not observed in the cold-resistant strain Ho_CR. To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduced in aging Ho_CS but sustained in non-aging Ho_CR. We also identified a deficient autophagy in Ho_CS epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly inducible autophagy flux upon proteasome inhibition. In the non- aging H. vulgaris animals, the blockade of autophagy by knocking down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.
Keywords Aging model system — Autophagy sensor — Epithelial stem cells — Hydra regeneration — Evolution of aging — p62/SQSTM1 — WIPI2 — Rapamycin
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Article (Published version) (27.3 MB) - public document Free access
Other version: http://dev.biologists.org/lookup/doi/10.1242/dev.177840
Dataset: https://hydratlas.unige.ch/blast/datasets/normacounts_CR2017.csv.gz; https:// hydratlas.unige.ch/blast/datasets/norma...
Structures
Faculté des sciences / Section de biologie / Département de génétique et évolution
Research group Groupe Galliot
Projects
Swiss National Science Foundation: 31003A_149630, 31003_169930
Autre: NIH R01AG037962
Citation
(ISO format) 		TOMCZYK, Szymon et al. Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra. In: Development, 2020, vol. 147, n° dev177840, p. 1-16. doi: 10.1242/dev.177840 https://archive-ouverte.unige.ch/unige:129365

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Deposited on : 2020-01-24

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