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Rapid and Efficient Conversion of Human Fibroblasts into Functional Neurons by Small Molecules
- Source :
- Stem Cell Reports, Stem Cell Reports, Vol 13, Iss 5, Pp 862-876 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Summary Recent studies have demonstrated that human astrocytes and fibroblasts can be directly converted into functional neurons by small molecules. However, fibroblasts, as a potentially better cell resource for transplantation, are not as easy to reprogram as astrocytes regarding their fate to neurons, and chemically induced neurons (iNs) with low efficiency from fibroblasts resulted in limited application for the treatment of neurological disorders, including depression. Here, we report that human fibroblasts can be efficiently and directly reprogrammed into glutamatergic neuron-like cells by serially exposing cells to a combination of small molecules. These iNs displayed neuronal transcriptional networks, and also exhibited mature firing patterns and formed functional synapses. Importantly, iNs could integrate into local circuits after transplantation into postnatal mouse brain. Our study provides a rapid and efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts. Furthermore, our approach offers strategies for disease modeling and drug discovery in central nervous system disorders.<br />Highlights • Small molecules efficiently reprogram human fibroblasts into glutamatergic neurons • iNs show neuronal transcriptional networks resembling that of human primary neurons • iNs can survive, mature, and integrate into local circuits after transplantation • P7C3-A20 is the most important component of the cocktail in the reprogramming process<br />In this article, Dai and colleagues show that human fibroblasts can be efficiently and directly reprogrammed into glutamatergic neuron-like cells by a combination of small molecules. These iNs displayed neuronal transcriptional networks, exhibited mature firing patterns and could also integrate into local circuits after transplantation. The study provides an efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts.
- Subjects :
- 0301 basic medicine
fibroblasts to neurons
Neurogenesis
Cell
Central nervous system
Mice, SCID
Biology
Biochemistry
glutamatergic neurons
Article
Cell Line
Small Molecule Libraries
03 medical and health sciences
Glutamatergic
0302 clinical medicine
Cell transplantation
Genetics
medicine
Animals
Humans
Cellular Reprogramming Techniques
cell transplantation
lcsh:QH301-705.5
Neurons
lcsh:R5-920
Drug discovery
Transcriptional Networks
Cell Biology
Fibroblasts
Cellular Reprogramming
Small molecule
direct reprogramming
Cell biology
Transplantation
small molecules
high efficiency
030104 developmental biology
medicine.anatomical_structure
nervous system
lcsh:Biology (General)
lcsh:Medicine (General)
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 22136711
- Volume :
- 13
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Stem Cell Reports
- Accession number :
- edsair.doi.dedup.....4d6f71145ac5685191b5e9fd52075365