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Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis

ABSTRACT: Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis

PROVIDER: PRJNA554666 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11551925.fastq.gz	Fastqsanger.gz
	SRR11551926.fastq.gz	Fastqsanger.gz
	SRR11551927.fastq.gz	Fastqsanger.gz
	SRR11551928.fastq.gz	Fastqsanger.gz
	SRR11551929.fastq.gz	Fastqsanger.gz

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Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Schmidtea mediterranea]

Project description:Lipid metabolism is recognized as a key process for stem cell maintenance and differentiation but genetic factors that instruct stem cell function by influencing lipid metabolism remain to be delineated. Here we identify Tnfaip2 as an inhibitor of reprogramming of mouse fibroblasts into induced pluripotent stem cells. Tnfaip2 knockout embryonic stem cells (ESCs) exhibit differentiation failure and knockdown of the planarian orthologue, Smed-exoc3, abrogates in vivo differentiation of somatic stem cells, tissue homeostasis, and regeneration. Tnfaip2 deficient ESCs fail to induce synthesis of cellular triacylglycerol (TAG) and lipid droplets (LD) coinciding with reduced expression of Vimentin (Vim) – a known inducer of LD formation. Knockdown of Vim and Tnfaip2 act epistatically in enhancing cellular reprogramming of mouse fibroblasts. Similarly, planarians devoid of Smed-exoc3 displayed acute loss of TAGs. Supplementation of palmitic acid (PA) and palmitoyl-L-carnitine (a mitochondrial carrier of PA) restores the differentiation capacity of Tnfaip2 deficient ESCs as well as stem cell differentiation and organ maintenance in Smed-exoc3-depleted planarians. Together, these results identify a novel pathway, which is essential for stem cell differentiation and organ maintenance by instructing lipid metabolism.

2020-11-16 | GSE134300 | GEO

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 1]

2020-11-16 | GSE134301 | GEO

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 2]

2020-11-16 | GSE148758 | GEO

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Schmidtea mediterranea]

Project description:Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Schmidtea mediterranea]

| PRJNA554667 | ENA

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 1]

Project description:Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 1]

| PRJNA554668 | ENA

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 2]

Project description:Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis [Mus musculus, 2]

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Tnfaip2/exoc3-driven lipid metabolism is essential for stem cell differentiation and organ homeostasis.

Project description:Lipid metabolism influences stem cell maintenance and differentiation but genetic factors that control these processes remain to be delineated. Here, we identify Tnfaip2 as an inhibitor of reprogramming of mouse fibroblasts into induced pluripotent stem cells. Tnfaip2 knockout impairs differentiation of embryonic stem cells (ESCs), and knockdown of the planarian para-ortholog, Smed-exoc3, abrogates in vivo tissue homeostasis and regeneration-processes that are driven by somatic stem cells. When stimulated to differentiate, Tnfaip2-deficient ESCs fail to induce synthesis of cellular triacylglycerol (TAG) and lipid droplets (LD) coinciding with reduced expression of vimentin (Vim)-a known inducer of LD formation. Smed-exoc3 depletion also causes a strong reduction of TAGs in planarians. The study shows that Tnfaip2 acts epistatically with and upstream of Vim in impairing cellular reprogramming. Supplementing palmitic acid (PA) and palmitoyl-L-carnitine (the mobilized form of PA) restores the differentiation capacity of Tnfaip2-deficient ESCs and organ maintenance in Smed-exoc3-depleted planarians. Together, these results identify a novel role of Tnfaip2 and exoc3 in controlling lipid metabolism, which is essential for ESC differentiation and planarian organ maintenance.

| S-EPMC7788457 | biostudies-literature

Tnfaip2/Exoc3 controls exit from pluripotency by mediating lipid droplet formation and FA-induced differentiation

Project description:The decline in stem cell function leads to impairments in tissue homeostasis but genetic factors that control differentiation and de-differentiation of stem cells in the context of tissue homeostasis remain to be delineated. Here we show that Tnfaip2 (a target gene of TNFa/NFkB signaling) has an essential role for the differentiation of pluripotent, embryonic stem cells (ESCs). Knockdown of the planarian pseudo-orthologue, Smed-exoc3, impairs pluripotent stem cell differentiation, tissue homeostasis and regeneration in vivo. The study shows that Tnfaip2 deletion impairs changes in lipid metabolism that drive differentiation induction of ESCs. The application of palmitic acid (PA, the most abundant saturated fatty acid in mammalian cells) and palmitoylcarnitine (a mitochondrial carrier of PA) fully restores the differentiation of ESCs as well as the differentiation of pluripotent stem cells and organ maintenance in Smed-exoc3-depleted planarians. Together, these results identify a novel pathway downstream of TNFa/NFkB signaling, which is essential for exit from pluripotency by mediating changes in lipid metabolism.

2020-11-18 | PXD014628 | Pride

Tnfaip2/Exoc3 driven lipid metabolism is essential for stem cell differentiation & organ homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-11-15 | GSE134302 | GEO

Adaptive cell invasion maintains organ homeostasis

Project description:Adaptive cell invasion maintains organ homeostasis

| PRJNA713403 | ENA