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Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation

ABSTRACT: Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation

PROVIDER: PRJNA756996 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15567300_1.fastq.gz	Fastqsanger.gz
	SRR15567300_2.fastq.gz	Fastqsanger.gz
	SRR15567301_1.fastq.gz	Fastqsanger.gz
	SRR15567301_2.fastq.gz	Fastqsanger.gz
	SRR15567302_1.fastq.gz	Fastqsanger.gz

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Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (scRNA-Seq)

Project description:Advances in 3D cell culture systems, including the hepatic organoids, has shown the potential to model the liver development in vitro. However, hepatocyte-like cells obtained by these means are still immature compared to the primary human hepatocytes. Here we applied single-cell RNA-seq and ATAC-seq to identify gene regulatory mechanisms distinct to mature human hepatocytes (in vivo) and organoid derived hepatocyte like cells (in vitro). Using a modified two-step perfusion protocol, primary hepatocytes from all lobular zones were obtained with high purity. Integrative analysis revealed a key role of transcription factors of the AP-1 family in cooperation with hepatocyte-specific transcription factors, such as HNF4A, in establishing cellular identity of mature hepatocytes. Furthermore, it revealed distinct transcription factor sets required/active in human hepatocytes and liver organoids. Function analysis of an organoid-enriched transcription factor ELF3, showed that decreased expression of ELF3 in liver organoids promotes increased expression of genes typical to mature hepatocytes. This study indicates that ELF3 functions as a barrier of hepatocyte differentiation from liver organoids. Collectively, our integrative analysis provides critical insights into the transcriptional regulatory networks of human hepatocytes and liver organoids, which will further efficient differentiation of functional hepatocytes in vitro.

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Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (RNA-Seq)

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Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (RNA-Seq)

Project description:Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (RNA-Seq)

| PRJNA756997 | ENA

Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (ATAC-Seq)

Project description:Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (ATAC-Seq)

| PRJNA756998 | ENA

Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (scRNA-Seq)

Project description:Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (scRNA-Seq)

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MicroRNA Expression profiles of mature hepatocytes and foetal liver progenitor cells

Project description:Human liver progenitor cells (LPCs) show therapeutic potential, however, their in vitro culture results in inadequate function and phenotypic instability reflecting incomplete understanding of in vivo processes. Foetal LPCs capable of differentiation to a hepatocyte phenotype were isolated and mRNA expression profiling carried out using Exiqon miRCURY microarrays. This was compared to profiles from mature human hepatocytes. Foetal LPCs exhibit a distinct miRNA profile consistent with a stem cell signature, cell division, and some liver-specific functions. 3 independent samples of second trimester liver progenitor cells were prolfiled along with 3 independent mature hepatocyte samples.

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