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Updated: May 6, 2026
Direct Lineage Reprogramming of Adult Mouse Fibroblast to Erythroid Progenitors
Published on: December 14, 2018
Direct lineage reprogramming of mouse fibroblasts to functional midbrain dopaminergic neuronal progenitors
Han-Seop Kim1, Janghwan Kim2, Yeonju Jo1
1Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
Abstract:
The direct lineage reprogramming of somatic cells to other lineages by defined factors has led to innovative cell-fate-change approaches for providing patient-specific cells. Recent reports have demonstrated that four pluripotency factors (Oct4, Sox2, Klf4, and c-Myc) are sufficient to directly reprogram fibroblasts to other specific cells, including induced neural stem cells (iNSCs). Here, we show that mouse fibroblasts can be directly reprogrammed into midbrain dopaminergic neuronal progenitors (DPs) by temporal expression of the pluripotency factors and environment containing sonic hedgehog and fibroblast growth factor 8. Within thirteen days, self-renewing and functional induced DPs (iDPs) were generated. Interestingly, the inhibition of both Jak and Gsk3β notably enhanced the iDP reprogramming efficiency. We confirmed the functionality of the iDPs by showing that the dopaminergic neurons generated from iDPs express midbrain markers, release dopamine, and show typical electrophysiological profiles. Our results demonstrate that the pluripotency factors-mediated direct reprogramming is an invaluable strategy for supplying functional and proliferating iDPs and may be useful for other neural progenitors required for disease modeling and cell therapies for neurodegenerative disorders.
Insights
Scientists reprogrammed mouse fibroblasts into functional dopaminergic neuronal progenitors (iDPs) using four key factors. Inhibiting Jak and Gsk3β significantly improved this direct lineage reprogramming for potential cell therapies.
Area of Science:
- Stem Cell Biology
- Neuroscience
- Regenerative Medicine
Background:
- Direct lineage reprogramming offers patient-specific cell sources.
- Four core pluripotency factors can reprogram fibroblasts into various cell types, including induced neural stem cells (iNSCs).
Purpose of the Study:
- To investigate the direct reprogramming of mouse fibroblasts into midbrain dopaminergic neuronal progenitors (DPs).
- To assess the efficiency and functionality of induced DPs (iDPs) generated through this method.
Main Methods:
- Temporal expression of Oct4, Sox2, Klf4, and c-Myc in mouse fibroblasts.
- Utilizing sonic hedgehog and fibroblast growth factor 8 in the culture environment.
- Testing the effect of Jak and Gsk3β inhibition on reprogramming efficiency.
Main Results:
- Generated self-renewing and functional induced dopaminergic neuronal progenitors (iDPs) within 13 days.
- Demonstrated that inhibiting Jak and Gsk3β significantly enhanced iDP reprogramming efficiency.
- Confirmed iDP functionality: derived dopaminergic neurons expressed midbrain markers, released dopamine, and exhibited electrophysiological activity.
Conclusions:
- Pluripotency factor-mediated direct reprogramming is effective for generating functional, proliferating iDPs.
- This strategy holds promise for disease modeling and cell therapies for neurodegenerative disorders.
- Further research into neural progenitor generation via direct reprogramming is warranted.
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