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Metabolic adaptations direct cell fate during tissue regeneration [crypts RNA-seq]

ABSTRACT: Metabolic adaptations direct cell fate during tissue regeneration [crypts RNA-seq]

PROVIDER: PRJNA1248980 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33095988_1.fastq.gz	Fastqsanger.gz
	SRR33095988_2.fastq.gz	Fastqsanger.gz
	SRR33095989_1.fastq.gz	Fastqsanger.gz
	SRR33095989_2.fastq.gz	Fastqsanger.gz
	SRR33095990_1.fastq.gz	Fastqsanger.gz

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Metabolic adaptations direct cell fate during tissue regeneration

Project description:Metabolic adaptations direct cell fate during tissue regeneration

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Metabolic adaptations direct cell fate during tissue regeneration [DMaKG_Mice_RNA-seq]

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Metabolic adaptations direct cell fate during tissue regeneration [Organoids_RNA-seq]

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Metabolic adaptations direct cell fate during tissue regeneration [crypts RNA-seq]

Project description:Although cell fate specification is generally attributed to transcriptional regulation, emerging data also indicate a role for molecules linked with intermediary metabolism. For example, α-ketoglutarate (αKG), which fuels energy production and biosynthetic pathways in the tricarboxylic acid (TCA) cycle, is also a co-factor for chromatin-modifying enzymes1-3. Nevertheless, whether TCA cycle metabolites regulate cell fate during tissue homeostasis and regeneration remains unexplored. In the intestine, we discovered unexpectedly heterogeneous expression of TCA cycle enzymes, with αKG dehydrogenase complex components4-6 upregulated in the absorptive lineage and downregulated in the secretory lineage. Using genetically modified mouse models and organoids, we demonstrated a dual, lineage-specific role for 2-oxoglutarate dehydrogenase (OGDH), the enzymatic subunit of αKG dehydrogenase complex. In the absorptive lineage, OGDH is upregulated by Hnf4 transcription factors to maintain the bioenergetic and biosynthetic needs of enterocytes. In the secretory lineage, OGDH is downregulated through a process that, when modeled, increases αKG levels and stimulates secretory cell differentiation. Consistent with this, in murine colitis models with impaired secretory cell number and maturation, OGDH inhibition or αKG supplementation reversed these impairments and promoted tissue healing. Hence, OGDH dependency is lineage-specific, and its regulation helps direct cell fate, offering insights for targeted therapies in regenerative medicine.

2025-04-10 | GSE294306 | GEO

Metabolic adaptations direct cell fate during tissue regeneration [shOGDH_Mice_RNA-seq]

2025-04-02 | GSE293286 | GEO

Metabolic adaptations direct cell fate during tissue regeneration [Organoids_RNA-seq]

2025-04-02 | GSE293285 | GEO

Metabolic adaptations direct cell fate during tissue regeneration [DMaKG_Mice_RNA-seq]

2025-04-02 | GSE293284 | GEO

Metabolic adaptations direct cell fate during tissue regeneration

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

2025-04-02 | GSE293287 | GEO

Gene expression data from DSS-treated crypts, normal colon crypts and tumor crypts

Project description:Comparative gene expression profiling between DSS-treated crypts and normal colon crypts Comparative gene expression profiling between normal colon crypts and tumor crypts

2017-01-01 | GSE56050 | GEO

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