Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a
| Autor: | Lin Cheng, Mengqing Xiang, Min Zou, Xuting Bian, Yanan Guo, Yulong Cai, Qinqin Deng, Dayu Sun, Min Zhang, Xiaoning Liu, Kangxin Jin, Haiwei Xu, Shuting Liu, Shengguo Li, Hongyu Zhong, Evelyn Shiang, Dongchang Xiao |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Science Cellular differentiation Notch signaling pathway General Physics and Astronomy Biology Hippocampus Article General Biochemistry Genetics and Molecular Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Alzheimer Disease Animals Homeostasis Humans Maze Learning lcsh:Science Transcription factor Progenitor Neurons Multidisciplinary Receptors Notch RBPJ fungi HEK 293 cells food and beverages Cell Differentiation General Chemistry Fibroblasts Cellular Reprogramming Neural stem cell Cell biology Mice Inbred C57BL Disease Models Animal Oligodendroglia HEK293 Cells 030104 developmental biology Astrocytes Female lcsh:Q Reprogramming 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-19 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Induced neural stem cells (iNSCs) reprogrammed from somatic cells have great potentials in cell replacement therapies and in vitro modeling of neural diseases. Direct conversion of fibroblasts into iNSCs has been shown to depend on a couple of key neural progenitor transcription factors (TFs), raising the question of whether such direct reprogramming can be achieved by non-neural progenitor TFs. Here we report that the non-neural progenitor TF Ptf1a alone is sufficient to directly reprogram mouse and human fibroblasts into self-renewable iNSCs capable of differentiating into functional neurons, astrocytes and oligodendrocytes, and improving cognitive dysfunction of Alzheimer’s disease mouse models when transplanted. The reprogramming activity of Ptf1a depends on its Notch-independent interaction with Rbpj which leads to subsequent activation of expression of TF genes and Notch signaling required for NSC specification, self-renewal, and homeostasis. Together, our data identify a non-canonical and safer approach to establish iNSCs for research and therapeutic purposes. Fibroblasts can be reprogrammed into induced neural stem cells (iNSCs) using transcription factors expressed in neural progenitors. Here the authors show that Ptf1a, which is normally expressed in postmitotic neurons, can reprogram fibroblasts to iNSCs through Notch independent interaction with Rbpj. |
| Databáze: | OpenAIRE |
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