In a pioneering feat, researchers have successfully converted adult human skin cells into neurons of the type that regulate appetite.To make the neurons, human skin cells were first genetically reprogrammed to become induced pluripotent stem (iPS) cells.
Like natural stem cells, iPS cells are capable of developing into any kind of adult cell when given a specific set of molecular signals in a specific order. The iPS cell technology has been used to create a variety of adult human cell types, including insulin-producing beta cells and forebrain and motor neurons.
"But until now, no one has been able to figure out how to convert human iPS cells into hypothalamic neurons," said study co-author Dieter Egli, senior research fellow at at the New York Stem Cell Foundation (NYSCF).
Hypothalamic neurons help regulate behavioural and basic physiological functions in the human body including, in addition to appetite, hypertension, sleep, mood and some social disorders. The team determined which signals are needed to transform iPS cells into arcuate hypothalamic neurons, a neuron subtype that regulates appetite.
The transformation process took about 30 days. The neurons were found to display key functional properties of arcuate hypothalamic neurons, including the ability to accurately process and secrete specific neuropeptides and to respond to metabolic signals such as insulin and leptin.
"These neurons are identical to natural hypothalamic neurons and will be useful for studying the neurophysiology of weight control, as well as molecular abnormalities that lead to obesity," explained senior author Rudolph L Leibel from Columbia University Medical Centre (CUMC).
In addition, the cells will allow us to evaluate potential obesity drugs in a way never before possible, he added.
The findings provide a patient-specific model for studying the neurophysiology of weight control and testing new therapies for obesity, concluded the paper that appeared in the Journal of Clinical Investigation.
In a separate study that appeared in the journal Development, a team from Harvard University have also succeeded in creating hypothalamic neurons from iPS cells. The investigators at Columbia and Harvard shared ideas during the course of the research and these studies are co-validating.
