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Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits (Capture C)

ABSTRACT: Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits (Capture C)

PROVIDER: PRJNA638300 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11964212_1.fastq.gz	Fastqsanger.gz
	SRR11964212_2.fastq.gz	Fastqsanger.gz
	SRR11964213_1.fastq.gz	Fastqsanger.gz
	SRR11964213_2.fastq.gz	Fastqsanger.gz
	SRR11964214_1.fastq.gz	Fastqsanger.gz

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Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits

Project description:Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits

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Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant common complex traits (Capture C)

Project description:To investigate the role of the hypothalamus in complex traits, we generated ATAC-seq, RNA-seq, and Promoter Focused Capture C to gain insight into the gene regulatory arcitecture contacting promoters in an embryonic stem cell dervived model of hypothalamic neuron differentiation

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Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits.

Project description:The hypothalamus regulates metabolic homeostasis by influencing behavior and endocrine systems. Given its role governing key traits, such as body weight and reproductive timing, understanding the genetic regulation of hypothalamic development and function could yield insights into disease pathogenesis. However, given its inaccessibility, studying human hypothalamic gene regulation has proven challenging. To address this gap, we generate a high-resolution chromatin architecture atlas of an established embryonic stem cell derived hypothalamic-like neuron model across three stages of in vitro differentiation. We profile accessible chromatin and identify physical contacts between gene promoters and putative cis-regulatory elements to characterize global regulatory landscape changes during hypothalamic differentiation. Next, we integrate these data with GWAS loci for various complex traits, identifying multiple candidate effector genes. Our results reveal common target genes for these traits, potentially affecting core developmental pathways. Our atlas will enable future efforts to determine hypothalamic mechanisms influencing disease susceptibility.

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