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Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

ABSTRACT: Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

PROVIDER: PRJNA762283 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15837448_1.fastq.gz	Fastqsanger.gz
	SRR15837448_2.fastq.gz	Fastqsanger.gz
	SRR15837449_1.fastq.gz	Fastqsanger.gz
	SRR15837449_2.fastq.gz	Fastqsanger.gz
	SRR15837450_1.fastq.gz	Fastqsanger.gz

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Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state

Project description:Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction during homeostasis. To experimentally address this concept, we generated intestinal epithelial cell (IEC)-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7?IEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape and proliferation rate remained unchanged in these mice. However, non-apoptotic cell extrusion was increased in Casp3/7?IEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single cell RNA sequences analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome composition and immune regulation.

2021-09-22 | GSE183885 | GEO

Executioner caspases 3 and 7 are dispensable for intestinal epithelium turnover and homeostasis at steady state.

Project description:Apoptosis is widely believed to be crucial for epithelial cell death and shedding in the intestine, thereby shaping the overall architecture of the gastrointestinal tract, but also regulating tolerance induction, pinpointing a role of apoptosis intestinal epithelial cell (IEC) turnover and maintenance of barrier function, and in maintaining immune homeostasis. To experimentally address this concept, we generated IEC-specific knockout mice that lack both executioner caspase-3 and caspase-7 (Casp3/7ΔIEC), which are the converging point of the extrinsic and intrinsic apoptotic pathway. Surprisingly, the overall architecture, cellular landscape, and proliferation rate remained unchanged in these mice. However, nonapoptotic cell extrusion was increased in Casp3/7ΔIEC mice, compensating apoptosis deficiency, maintaining the same physiological level of IEC shedding. Microbiome richness and composition stayed unaffected, bearing no sign of dysbiosis. Transcriptome and single-cell RNA sequencing analyses of IECs and immune cells revealed no differences in signaling pathways of differentiation and inflammation. These findings demonstrate that during homeostasis, apoptosis per se is dispensable for IEC turnover at the top of intestinal villi intestinal tissue dynamics, microbiome, and immune cell composition.

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A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast

Project description:Cells have compensatory mechanisms to coordinate the rates of major biological processes, thereby permitting growth in a wide variety of conditions. Here, we uncover a compensatory link between cleavage/polyadenylation in the nucleus and mRNA turnover in the cytoplasm. On a global basis, same-gene 3’ mRNA isoforms with > two-fold differences in half-lives have steady-state mRNA levels that differ by significantly less than a factor of two. In addition, increased efficiency of cleavage/polyadenylation at a specific site is associated with reduced stability of the corresponding 3’ mRNA isoform. This inverse relationship between cleavage/polyadenylation and mRNA isoform half-life reduces the variability in the steady-state levels of mRNA isoforms, and it occurs in all four growth conditions tested. These observations suggest that during cleavage/polyadenylation in the nucleus, mRNA isoforms are marked in a manner that persists upon translocation to the cytoplasm and affects the activity of mRNA degradation machinery, thus influencing mRNA stability.

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A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast

Project description:A compensatory link between cleavage/polyadenylation and mRNA turnover regulates steady-state mRNA levels in yeast

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Project description:We obtained a spatial measurement of RNA and Proteins in the small intestinal epithelium along the crypt-villus axis. We found that both were spatially heterogeneous, yet often spatially anti-correlated. We developed a Bayesian approach to infer protein translation and degradation rates from the combined spatial profiles, and demonstrate that space-independent protein-synthesis delays can explain the mRNA-protein discordances. Our work provides a proteomic spatial blueprint of the Intestinal epithelium and highlights the importance of protein measurements for inferring states of tissue cells that operate outside of steady state

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Loss of executioner caspases-3 and -7 in intestinal epithelial cells is dispensable but can be compensated allowing normal gut homeostasis

Project description:Loss of executioner caspases-3 and -7 in intestinal epithelial cells is dispensable but can be compensated allowing normal gut homeostasis

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Growth rate controls mRNA turnover in steady and non-steady states.

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