A new stem cell advance | Harvard Gazette

Collaborating with scientists from New York, Toronto, and Tokyo, Harvard Stem Cell Institute (HSCI) researchers have devised two methods for using stem cells to generate the type of neurons that help regulate behavioral and basic physiological functions in the human body, such as obesity and hypertension, as well as sleep, mood, and some social disorders.

The work by Florian Merkle, Kevin Eggan, Alex Schier, and colleagues provides researchers, for the first time, with live hypothalamic neurons to use as targets for drug discovery and therapeutic cell-transplantation efforts for conditions related to stress, reproduction, puberty, and immune function, as hypothalamic neurons are often involved in those diseases as well.

Not only is this exciting because of the science involved, said Merkle, 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, said Merkle. Its very conserved, and thats because it plays such a basic function. Though it makes up only about 0.3 percent of the adult human brain, the hypothalamus serves as a regulator for numerous basic physiological functions.

Thus far, research exploring the origin or process of hypothalamic dysfunction has been limited because researchers havent been able to observe live hypothalamic cells.

Merkle and a team of scientists from HSCI, New Yorks Sloan Kettering Institute for Cancer Research, Torontos Hospital for Sick Children, and Japans RIKEN developed the two neuron-generating methods, self-patterning and directed differentiation, concurrently.

The new work has been published in the journal Development.

In his self-patterning approach, 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.

When asked how the two processes differed, Merkle said that during directed differentiation the researchers are pushing [stem] cells very strongly, guiding them toward a particular fate, and not relying on them to do it themselves. Merkle used small molecules to steer stem cell differentiation down a specific pathway.

I think that there is definitely more opportunity to explore and refine directed differentiation to make different regions within the hypothalamus, said Merkle.

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A new stem cell advance | Harvard Gazette