Generating hypothalamic neurons from human pluripotent stem cells

nerves

Source: Pixabay

The field of stem cells is booming. Every other day there is a new study being conducted on stem cells and how they can be used for various therapies. A recent study published in Development talks about how neuropeptidergic hypothalamic neurons can be generated in the laboratory from human pluripotent stem cells.

Hypothalamic neurons are important for physiological and behavioral processes via secreted neuropeptides. These neurons play a role in obesity, narcolepsy and infertility.

Scientists from New York, Toronto, and Tokyo, and Harvard Stem Cell Institute (HSCI) researchers have devised two methods for using stem cells to generate hypothalamic neurons. The researchers were able to differentiate human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone.

This could enable researchers to use for the first time, live hypothalamic neurons to use as targets for drug discovery and for therapeutic cell-transplantation efforts for conditions such as stress, reproduction, puberty and immune function, in which hypothalamic neurons are often involved.

Image: Hypothalamic neurons created from stem cells

Image: Hypothalamic neurons created from stem cells

“Not only is this exciting because of the science involved,” said Florian T. Merkle, the lead author of the paper and a postdoctoral fellow in the lab of HSCI principal faculty member Kevin Eggan, who pioneered disease in a dish technology, “but by being able to produce this one type of neuron we bring possible treatments for a wide range of conditions closer to the clinic. The hypothalamus is an ancient structure of the brain. It’s very conserved, and that’s because it plays such a basic function.”

Merkle put 5,000 stem cells in a dish amid an environment conducive to survival and left them alone. Within a day, the cells would aggregate and “communicate with each other” to plan which stem cells would differentiate into which neural progenitors. The aggregate eventually differentiated into cells that, together, made a tissue-like structure similar to the hypothalamus.

“It really has not been possible to study these neurons before, and now we have an opportunity to do that,” said Merkle. “A lot has been done in mouse cells, but we don’t know how similar [to human cells] they really are. There could be important differences that are relevant to human disease. There is a universe of diseases out there, and our ability to study them using these stem cells is fundamentally limited by our ability to make those cell types in a dish.”

The original paper can be accessed here.

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