Neuronal Progenitors

Introduction of Neuronal Progenitors

Neuronal progenitors refer to the progenitor cells of the central nervous system (CNS) that produce glial and multiple neuronal cell types to populate the CNS. Generally speaking, the neuronal progenitors exist in the CNS of developing embryos, as well as the neonatal and mature adult brain. Based on their location, morphology, gene expression profile, time distribution, and functions in the brain, the neuronal progenitors present different characteristics.

Fig.1 Differentiation potential of neural progenitor cells derived from human embryonic stem cells. (Noisa, 2015)

Introduction of hES-NP Cells

With the ability to differentiate into different kinds of cell types, the human embryonic stem cells (hESCs) have been widely used to develop cell-based therapies against multiple neurodegenerative disorders, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease. Some studies have shown that hESCs can be induced to neural progenitor cells by Dorsomorphin, which is a small molecule that inhibits BMP signaling. The obtained neural progenitor cells present neurobipolarity, high expression of neural progenitor genes, and multipotential differentiation ability.

Fig.2 Schematic of differentiation conditions for DA neurons from neural progenitors. (Noisa, 2015)

Based on the characteristics of stereotyping and proliferation, the hES-NP cells can be used as a scalable source to produce various types of neurons and glial cells, for toxicant and drug screening, and ultimately for cell-based alternative therapies. SHH and FGF8 are important dopaminergic (DA) neuron inducers, the DA neurons can be obtained from hES-NP cells following the exposure of SHH and FGF8. And its differentiation efficiency can be improved with LMX1A, a recombinant midbrain factor. In addition, better culture systems and microenvironments can further increase differentiation efficiency. The CBF1 and bFGF responsiveness showed that these hES-NPs are similar to embryonic neural progenitor cells. Besides DA neurons, a variety of neuronal subtypes can be obtained from hES-NP cells which include but are not limited as follow:

• Sensory neurons
• GABAergic neurons
• Dopaminergic neurons
• Cholinergic neurons
• Cerebral cortical neurons
• Striatal neurons
• Motor neurons

Characteristics of hES-NP Cells

• Stability in a long-term culture
• Ability to produce neurons and glia
• Expression of neural progenitor markers

Neuronal Progenitors in Developing Mammalian Neocortex

During embryonic neuro development, the proliferation of neuronal progenitors is largely regulated by a series of soluble factors, such as bFGF and EGF. These two factors are essential at different stages of brain development. Based on cell biology, there are three types of neuronal progenitors that exist in the developing mammalian neocortex, which include apical progenitors, basal progenitors, and subapical progenitors.

• Apical Progenitors (APs) - It has been described that there are three types of APs, including neuroepithelial cells, the derivative apical radial glia, and apical intermediate progenitors.
• Basal Progenitors (BPs) - There are two types of BPs distinguished as basal intermediate progenitors and basal radial glia, both of them can be obtained from APs or BPs themselves.
• Subapical Progenitors (SAPs) - Similar to BPs, SAPs undergo mitosis at an abventricular location.

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References

1. Noisa, P.; et al. Neural progenitor cells derived from human embryonic stem cells as an origin of dopaminergic neurons. Stem cells international. 2015, 2015.
2. Florio, M.; Huttner, W. Neural progenitors, neurogenesis and the evolution of the neocortex. Development. 2014, 141(11): 2182-2194.

For Research Use Only. Not For Clinical Use.