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Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions

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Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.

Liheng Wang^1,2, Dieter Egli^1,2,3, Rudolph L Leibel^1,2

¹Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York.

Current Protocols in Human Genetics

|July 2, 2016

Summary

Scientists developed a new method to create arcuate-like hypothalamic neurons from human pluripotent stem cells. This breakthrough aids obesity research by providing accessible human hypothalamic neurons for study.

Keywords:

ARC neurons feeder-free human pluripotent stem cells hypothalamic neurons

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Efficient Derivation of Human Neuronal Progenitors and Neurons from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

Efficient Derivation of Human Neuronal Progenitors and Neurons from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

Published on: October 28, 2011

Area of Science:

Neuroscience
Stem Cell Biology
Endocrinology

Background:

The hypothalamus regulates body weight, but human hypothalamic cells are difficult to study.
Understanding hypothalamic cellular physiology is key to addressing obesity pathogenesis.

Purpose of the Study:

To develop a method for generating arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells.
To provide a model for studying human hypothalamic neurons relevant to obesity.

Main Methods:

Utilized specific signaling pathways (SHH activation, BMP/TGFβ inhibition) to guide hPS cell differentiation into NKX2.1+ hypothalamic progenitors.
Employed timed NOTCH inhibition and BDNF incubation for maturation into pro-opiomelanocortin and neuropeptide Y neurons.
Characterized the generated neurons for molecular and cellular consistency with native arcuate neurons.

Main Results:

Successfully generated hypothalamic progenitors from hPS cells using a defined signaling protocol.
Differentiated and matured these progenitors into functional arcuate-like neurons expressing key neuropeptides.
Confirmed that the generated neurons possess molecular and cellular features characteristic of the human arcuate hypothalamus.

Conclusions:

A novel and efficient protocol for deriving arcuate-like neurons from hPS cells has been established.
This method overcomes the inaccessibility of primary human hypothalamic cells for research.
The generated neurons serve as a valuable tool for investigating hypothalamic function and obesity.