Identify transcriptional regulators of Mc4r in the hypothalamus
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ABSTRACT:
PROVIDER: PRJNA1031152 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identify transcriptional regulators of Mc4r in the hypothalamus [RNA-Seq]
| PRJNA1024903 | ENA
Project description:Identify transcriptional regulators of Mc4r in the hypothalamus [scRNA-Seq]
| PRJNA1031370 | ENA
Project description:Identify transcriptional regulators of Mc4r in the hypothalamus [ATAC-Seq]
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Project description:Human MC4R mutations can increase or decrease obesity risk. Other than intracellular signaling, MC4R function is also influenced by its levels. However, the genetic programs that govern MC4R transcription in the brain remain largely unknown. Moreover, it is unclear whether human genetic variants exist that affect Mc4r expression and obesity risk. Here, we identify the homeodomain transcription factor Otp as one regulator of Mc4r expression in a specific subset of hypothalamic neurons. Selective loss of Otp in these neurons during development or adulthood results in reduced Mc4r expression and excessive body weight gain. Moreover, OTP interacts with upstream regulatory sequences of Mc4r to modulate its transcription.
2025-01-15 | GSE244790 | GEO
Project description:Human MC4R mutations can increase or decrease obesity risk. Other than intracellular signaling, MC4R function is also influenced by its levels. However, the genetic programs that govern MC4R transcription in the brain remain largely unknown. Moreover, it is unclear whether human genetic variants exist that affect Mc4r expression and obesity risk. Here, we identify the homeodomain transcription factor Otp as one regulator of Mc4r expression in a specific subset of hypothalamic neurons. Selective loss of Otp in these neurons during development or adulthood results in reduced Mc4r expression and excessive body weight gain. Moreover, OTP interacts with upstream regulatory sequences of Mc4r to modulate its transcription.
2025-01-15 | GSE246034 | GEO
Project description:Human MC4R mutations can increase or decrease obesity risk. Other than intracellular signaling, MC4R function is also influenced by its levels. However, the genetic programs that govern MC4R transcription in the brain remain largely unknown. Moreover, it is unclear whether human genetic variants exist that affect Mc4r expression and obesity risk. Here, we identify the homeodomain transcription factor Otp as one regulator of Mc4r expression in a specific subset of hypothalamic neurons. Selective loss of Otp in these neurons during development or adulthood results in reduced Mc4r expression and excessive body weight gain. Moreover, OTP interacts with upstream regulatory sequences of Mc4r to modulate its transcription.
2025-01-15 | GSE244791 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-15 | GSE246035 | GEO
Project description:Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting. Experiment Overall Design: Gilts (n=24; 12 wildtype and 12 homozygous for D298N) were either fed ad libitum or fasted for 3 days in a completely randomized complete block design with a 2x2 factorial treatment structure.
2009-04-25 | E-GEOD-13528 | biostudies-arrayexpress
Project description:The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies. Here, we combine single-nucleus sequencing of 433,369 human hypothalamic cells with spatial transcriptomics, generating a comprehensive spatio-cellular transcriptional map of the hypothalamus, the ‘HYPOMAP’. Whilst conservation of neuronal cell types between humans and mice, based on transcriptomic identity, is generally high, there are notable exceptions. Specifically, there are significant disparities in the identity of POMC neurons and in the expression levels of GPCRs between the two species that carry direct implications for currently approved obesity treatments. Out of the 452 hypothalamic cell types, we find 291 neuronal clusters are significantly enriched for expression of BMI GWAS genes. This enrichment is driven by 426 ‘effector’ genes. Rare deleterious variants in 6 of these, MC4R, PCSK1, POMC, CALCR, BSN and CORO1A, associate with BMI at population level, and CORO1A has not previously been linked to BMI. Thus, HYPOMAP provides a detailed atlas of the human hypothalamus in a spatial context and serves as an important resource to identify novel druggable targets for treating a wide range of conditions, including reproductive, circadian, and metabolic disorders.
2025-01-29 | GSE278848 | GEO
Project description:Engineering transcriptional regulators using REPLACE
| PRJNA1133800 | ENA