Researchers use embryonic stem cells model to study the genetic structure of the hypothalamus

Researchers at the Children’s Hospital of Philadelphia (CHOP), discovered that several genes are involved in a variety of bodily functions related to the hypothalamus. This region of the brain is notoriously difficult to study. The findings could be used to help medical professionals identify the root of dysfunction in many important aspects controlled by the hypothalamus (e.g. sleep and reproduction, stress, and so on.).

The research findings were published today by Nature Communications.

The hypothalamus helps maintain healthy and stable metabolism by influencing a variety of vital functions, such as appetite and thirst as well as puberty and reproductive timing, sleep cycles, and body temperature. However, the hypothalamus located in the center of the brain, which makes it difficult to analyze the gene regulation associated with these traits.

The researchers designed an embryonic stem cell model (ESC) to study gene expression during the hypothalamus’s development. This model allowed them examine the genetic structure of hypothalamic progenitor cells, cells that were not yet fully developed into hypothalamus cells. Next, they studied hypothalamic neurons with arcuate nucleus-like hypothalamic cells. Researchers looked at genome-wide association information (GWAS) from various hypothalamus neuron types to identify genes that govern particular traits regulated in the hypothalamus.

We can observe how the hypothalamus develops as time passes by studying the three-dimensional genome architecture of these models of cells. This study provided us with more concrete information regarding hypothalamic diseases.

Struan F.A. Grant, PhD Senior author, Director of Spatial and Functional Genomics and Daniel B. Burke Endowed chair for Diabetes Research at CHOP

Grant and his colleagues analyzed the puberty-related variants and body mass index height, bipolar disorder, sleep and major depressive disorder, among others. They discovered both novel and well-known genes that are linked to these characteristics. For example, their data confirmed the significance of the BDNF of gene in the development of body mass index and obesity risk. Another gene that was of interest in the study was PER2 which is implicated in sleep regulation.

The data gathered during the study will be made public. A lot of the diseases studied could be caused by different factors, and the results will help researchers determine which genes play a more central role in this tissue and ultimately, inform the the clinical practice. Genetic variations that affect the body mass index, like those in hypothalamus and fat tissue cells could cause it to be affected. This will allow for more customized treatment options.

“The data set we created from this study will allow other researchers to identify which conditions or diseases are relevant to an analysis of the genetics of the patient,” Grant said. “As more information is available about the hypothalamus this data set can be compared to the data set and possibly identify therapeutic targets for multiple disorders.”

Journal reference:

Pahl M.C., Pahl M.C.. (2021). Cis-regulatory architecture for human ESC-derived hypothalamic neurons differentiation assists in variant to gene mapping of complex traits that are relevant to the gene. Nature Communications.

Content Source:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

Related Articles