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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (snRNAseq)

ABSTRACT: To investigate the efect of extracellular bilirubin and intracellular ascorbate on the development of zonal hepatocytes in human liver organoids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222648 | GEO | 2024/09/18

REPOSITORIES: GEO

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (ChIPseq)

Project description:To investigate the efect of extracellular bilirubin and intracellular ascorbate on the development of zonal hepatocytes in human liver organoids.

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (RNA-seq)

Project description:To investigate the efect of extracellular bilirubin and intracellular ascorbate on the development of zonal hepatocytes in human liver organoids

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (snRNAseq)

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity

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

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Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (ChIPseq)

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NFI transcription factors regulate zonal olfactory receptor expression

Project description:Expression of one out of > 1000 olfactory receptor (OR) genes is stochastic, yet organized into anatomic "zones" along the dorsoventral axis of the olfactory epithelium. Here we profile the gene expression, chromatin state and nuclear architecture of olfactory sensory neurons and olfactory progenitors of different zones. We discovered that zonal OR expression is specified by two processes: low-level polygenic transcription of OR genes in olfactory progenitors, as wells as the chromatin structure and nuclear architecture during olfactory differentiation. Specifically, in cells of any zonal segment, polygenic transcription in olfactory progenitors defines the OR repertoire eligible for OR choice as the cells mature, while an increased level of heterochromatin and chromatin compaction represses ectopic more dorsally expressed ORs. We find that this process is regulated by the NFI family of transcription factors that are expressed in a graded fashion in the olfactory epithelium. Conditional deletion of NFI A, B, and X results in a transformation of the chromatin state and nucellar architecture and an accompanying shift in the preferred OR repertoire.

2023-06-14 | GSE158730 | GEO

T-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism.

Project description:β-catenin signaling can be both a physiological and an oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20 to 40% of hepatocellular carcinomas with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by Tcf4 and β-catenin, their transcriptome and their metabolome. We find that Tcf4 DNA-bindings depend on β-catenin. Tcf4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf4 on Hnf4-responsive elements. β-catenin, Tcf4 and Hnf4α interact, dictating β-catenin transcription which is antagonistic to that elicited by Hnf4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. We conclude that β-catenin patterns the zonal liver together with Tcf4, Hnf4α and xenobiotic nuclear receptors. This network represses lipid metabolism, and exacerbates glutamine, drug and bile metabolism, mirroring hepatocellular carcinomas with β-catenin mutational activation. In vivo liver samples in 4 conditions: Betacat activated (WCE, Tcf4 chipseq, Betacat chipseq, mRNAseq with 2 replicates), Betacat null (WCE, Tcf4 chipseq, mRNAseq with 2 replicates), Betacat control (mRNAseq with 2 replicates), Wild type (mRNAseq with 2 replicates)

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NFI transcription factors regulate zonal olfactory receptor expression

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