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Autophagy maintains intestinal stem cell integrity

ABSTRACT: Autophagy maintains intestinal stem cell integrity

PROVIDER: PRJNA564106 | ENA |

REPOSITORIES: ENA

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Autophagy maintains intestinal stem cell integrity

Project description:The intestinal epithelium is continuously renewed by a pool of intestinal stem cells expressing Lgr5. We show that deletion of the key autophagy gene Atg7 affects the survival of Lgr5+ intestinal stem cells. Mechanistically, this involves defective DNA repair, oxidative stress, and altered interactions with the microbiota. This study highlights the importance of autophagy in maintaining the integrity of intestinal stem cells.

2020-05-28 | GSE136952 | GEO

The Tif1Beta-Hp1 system maintains transcriptional integrity of hematopoietic stem cells

Project description:The Tif1Beta-Hp1 system maintains transcriptional integrity of hematopoietic stem cells

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Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

Project description:The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity.

2019-09-12 | PXD014829 | Pride

MYTHO: a novel regulator of skeletal muscle autophagy and integrity

Project description:Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.

2023-01-20 | GSE222885 | GEO

Hormone-responsive Bmpr1a maintains myoepithelial integrity during pregnancy

Project description:Hormone-responsive Bmpr1a maintains myoepithelial integrity during pregnancy

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Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis

Project description:Atr maintains chromosomal integrity during postnatal cerebellar neurogenesis

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Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells

Project description:Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells

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BRCA1 maintains telomere integrity through suppression of TERRA RNA and TERRA R-loop-induced DNA damage

Project description:Data in support of Vohhodina et al. "BRCA1 maintains telomere integrity through suppression of TERRA RNA and TERRA R-loop-induced DNA damage"

2021-04-21 | MSV000087276 | MassIVE

Autophagy maintains stem cells and intestinal homeostasis in Drosophila.

Project description:Intestinal homeostasis is maintained by tightly controlled proliferation and differentiation of tissue-resident multipotent stem cells during aging and regeneration, which ensures organismal adaptation. Here we show that autophagy is required in Drosophila intestinal stem cells to sustain proliferation, and preserves the stem cell pool. Autophagy-deficient stem cells show elevated DNA damage and cell cycle arrest during aging, and are frequently eliminated via JNK-mediated apoptosis. Interestingly, loss of Chk2, a DNA damage-activated kinase that arrests the cell cycle and promotes DNA repair and apoptosis, leads to uncontrolled proliferation of intestinal stem cells regardless of their autophagy status. Chk2 accumulates in the nuclei of autophagy-deficient stem cells, raising the possibility that its activation may contribute to the effects of autophagy inhibition in intestinal stem cells. Our study reveals the crucial role of autophagy in preserving proper stem cell function for the continuous renewal of the intestinal epithelium in Drosophila.

| S-EPMC5854693 | biostudies-other

Autophagy protects integrity of tumor suppressors from replication stress

Project description:Autophagy protects integrity of tumor suppressors from replication stress

| PRJNA767834 | ENA