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Low-density Lipoprotein Regulates Intestinal Stem Cell Homeostasis via PPAR Pathway

ABSTRACT: Low-density Lipoprotein Regulates Intestinal Stem Cell Homeostasis via PPAR Pathway

PROVIDER: PRJNA1120831 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29307513.fastq.gz	Fastqsanger.gz
	SRR29307514.fastq.gz	Fastqsanger.gz
	SRR29307515.fastq.gz	Fastqsanger.gz
	SRR29307516.fastq.gz	Fastqsanger.gz
	SRR29307517.fastq.gz	Fastqsanger.gz

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Low-density Lipoprotein Regulates Intestinal Stem Cell Homeostasis via PPAR Pathway

Project description:Epidemiological studies have highlighted a strong association between hyperlipidemia and an increased risk of cancer in the gut. Intestinal stem cells (ISCs) have been demonstrated as the cells of origin for tumorigenesis in the gut. However, the impact of hyperlipidemia on ISC homeostasis remains unclear. Here, we show that hyperlipidemia induced by low-density lipoprotein receptor (Ldlr) deficiency enhances ISC proliferation in vivo. Additionally, LDL treatment impairs organoid survival but increases ISC stemness ex vivo, as evidenced by the formation of poorly differentiated spheroid and higher ISC self-renewal capacity. Mechanistically, LDL treatment activates PPAR pathways, and pharmacological inhibition of PPAR and its downstream targets, including CPT1A and PDK4, mitigates the effect of LDL on ISCs. Furthermore, although Ldlr-/- intestines exhibit increased susceptibility to irradiation-induced crypt damage, they regenerate completely within a similar timeframe as controls. These findings demonstrate that hyperlipidemia modulates ISC homeostasis, providing new insights into the mechanism linking hyperlipidemia with tumorigenesis in the gut.

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The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice

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Retinal gene expression of low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice

Project description:Retinal gene expression was assessed from postnatal day (P) 8 old low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice with a Illumina mouse-WG6 expression BeadChip. RNA was extracted from the retinas of P8 Lrp5 knockout and wild type mice (n=3 each group). Total RNA (1ug each) were reverse transcribed, followed by a single in vitro transcription amplification to incorporate biotin-labeled nucleotide, and subsequent hybridization and staining with strepatavidin-Cy3 according to the manufacturer’s instructions.

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Project description:The aim of this study was to identify novel genes and pathways underlying lipoprotein homeostasis. The liver expression profile of mild hyperlipidemic E3L transgenic mice was compared to that of the wild-type B6 mice. Keywords: parallel sample

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A sexually dimorphic hepatic cycle of very low density lipoprotein uptake and assembly

Project description:A sexually dimorphic hepatic cycle of very low density lipoprotein uptake and assembly

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