Generation of human Neuronal restricted progenitors by GIBH scientists
Recently, a research group led by Prof. Liangxue Lai has successfully transdifferentiated human fetal fibroblasts into human Neuronal Restricted Progenitors (hiNRPs). The hiNRPs can proliferate and differentiate specifically into terminal neurons but not glial cells. This work had been published online by Journal of Biological Chemistry.
Terminal-differentiated neurons have been directly induced from fibroblasts. However, these cells were, only few cells could survive and play functions due to their limited ability to proliferate when transplanted into host, resulted in the treatment effectiveness of iN transplantation is not ideal. Many studies have focused on the generation of multi-lineage neural stem cells (NSCs). NSCs can differentiate into neurons and glial cells. However, studies show that NSCs are more likely to differentiate into glial cells rather than functional neurons after transplantation, which is a disadvantage for neuron-replacement therapy of neurodegenerative diseases.
Neuronal restricted progenitors (NRPs) represent a type of transitional intermediate cells that lie between multipotent neural progenitors and terminal differentiated neurons during neurogenesis. These NRPs have the ability to self-renew and differentiate into neurons, but not into glial cells, which is considered as an advantage over neural stem cells for cellular therapy of human neurodegenerative diseases. However, difficulty in the extraction of highly purified NPRs from normal nervous tissue prevents further studies and applications. Prof.Lai’s research team reported conversion of human fetal dermal fibroblasts into human induced neuronal restricted progenitors (hiNRPs) in eleven days by using just three defined factors: Sox2, c-Myc, and either Brn2 or Brn4. The hiNRPs exhibited distinct neuronal characteristics and can differentiate into various terminal neurons, but not any glial cells.
The generation of hiNRPs from somatic cells will provide a new source of cells for cellular replacement therapy of human neurodegenerative diseases.