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Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption [scRNA-Seq]

ABSTRACT: Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption [scRNA-Seq]

PROVIDER: PRJNA961211 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24293582_1.fastq.gz	Fastqsanger.gz
	SRR24293582_2.fastq.gz	Fastqsanger.gz
	SRR24293583_1.fastq.gz	Fastqsanger.gz
	SRR24293583_2.fastq.gz	Fastqsanger.gz
	SRR24293584_1.fastq.gz	Fastqsanger.gz

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Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption

Project description:Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption

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Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption [RNA-Seq]

Project description:Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function mutations. We elucidate the pathogenesis of limb reduction in an Esco2fl/fl;Prrx1-CreTg/0 mouse model using bulk- and single cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with the p53 inhibitor pifithrin-α, identified using a drug repositioning approach, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and human limb reduction disorders, suggesting etiological commonalities of cell death and vascular defects.

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Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption [scRNA-Seq]

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Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption

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