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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 (RNA-Seq)

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

PROVIDER: PRJNA638301 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11964259_1.fastq.gz	Fastqsanger.gz
	SRR11964259_2.fastq.gz	Fastqsanger.gz
	SRR11964260_1.fastq.gz	Fastqsanger.gz
	SRR11964260_2.fastq.gz	Fastqsanger.gz
	SRR11964261_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 (ATAC-Seq)

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

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

| PRJNA638300 | ENA

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

Project description:To investigate the role of the hypothalamus in influencing 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 common complex traits (ATAC-Seq)

2021-10-01 | GSE152090 | GEO

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.

| S-EPMC8604959 | biostudies-literature

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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Project description:The central nervous system (CNS) hypothalamus controls systemic metabolism. Inflammatory CNS processes evolving upon exposure to calorie-rich diet are thought to promote impaired metabolic CNS control, thereby triggering obesity and Type-2 diabetes (T2D). However, immune cells relevant for maintaining hypothalamic integrity remain incompletely understood. Here, we identify hypothalamic CD4+Foxp3+regulatory T(Treg) cells which control local tissue-inflammation. Specifically, upon exposure to a calorie-rich diet, a significant decline in hypothalamus-residing Foxp3+Tregs occurred and was accompanied by increased immune activation of CD4+T cells, infiltrating macrophages and microglia. Microglial proteomes of mice exposed to the hypercaloric challenge confirmed characteristics of immune activation; specifically, mRNA expression profiling of hypothalamic CD4+T cells indicated a Th1-mediated inflammatory state evidenced by high levels of Tbx21, Cxcr3, Cd226 and reduced expression of Ccr7 and S1P1 receptors relevant for recruitment to and retention at inflammatory sites. Using Treg depletion and transfer experiments in vivo, we found that Foxp3+Tregs critically limit hypothalamic immune activation induced by hyper-caloric challenge. Our findings open new avenues in the design of tailored concepts to improve immunometabolic health in obesity and T2D.

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