Appetite-regulating neurons are derived from skin cells
Researchers at Columbia University Medical Center, working under the guidance of Professor Rudolph L. Leibel, have successfully transformed adult human skin cells into specialized neurons that perform the function of regulating appetite. Such cells can be used as a personalized model for studying the neurophysiology of body weight changes, as well as for testing experimental methods of treating obesity.
According to Professor Leibel, mice are a good model for studying obesity, but human cells are a more suitable model for research purposes. Unfortunately, appetite–regulating cells are localized in an inaccessible region of the brain - the hypothalamus. For this reason, until now, scientists had to be content with mouse models or human cells obtained during autopsy, which significantly limited the possibilities of studying the fundamental aspects of human obesity.
To obtain the desired neurons, skin cells obtained from patients with monogenetic forms of obesity, such as Bardet-Bidl syndrome (which, in addition to obesity, causes many disorders in the development of the body), were first subjected to genetic reprogramming in order to obtain induced pluripotent stem cells (iPSCs). Previously, such cells were successfully used to produce various types of cells of the adult body, but so far no one has been able to turn them into hypothalamic neurons.
The authors have developed a scheme of sequential exposure to molecular stimuli that ensures the transformation of iPSCs into arched neurons of the hypothalamus that perform the function of regulating appetite. The entire transformation process took 30 days. The resulting cells possessed all the key properties demonstrated in culture by the arched neurons of the hypothalamus of mice, including the ability to synthesize and secrete specific neuropeptides. They also responded to metabolic signals, such as changes in the levels of the hormones insulin and leptin, and expressed markers characteristic of hypothalamic neurons, such as proopiomelanocortin, neuropeptide Y, agouti-linked peptide, somatostatin and dopamine.
The authors note that the cells they obtained are not completely identical to the neurons of the hypothalamus, but they are very close to them and will become a useful tool in studying the neurophysiology of body weight changes, as well as molecular disorders leading to the development of obesity. Moreover, this cellular model will allow us to evaluate the effectiveness of new anti-obesity drugs with unprecedented accuracy.
Article by Liheng Wang et al. Differentiation of hypothalamic-like neurons from human pluripotent stem cells is published in the Journal of Clinical Investigation.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Columbia University Medical Center:
Neurons Controlling Appetite Made from Skin Cells.
03.03.2015