Abstract
Direct cellular reprogramming exhibits distinct advantages over reprogramming from an induced pluripotent stem cell intermediate. These include a reduced risk of tumorigenesis and the likely preservation of epigenetic data. In vitro direct reprogramming approaches primarily aim to model the pathophysiological development of neurological disease and identify therapeutic targets, while in vivo direct reprogramming aims to develop treatments for various neurological disorders, including cerebral injury and cancer. In both approaches, there is progress toward developing increased control of subtype-specific production of induced neurons. A majority of research primarily utilizes fibroblasts as the donor cells. However, there are a variety of other somatic cell types that have demonstrated the potential for reprogramming into induced neurons. This review highlights studies that utilize non-fibroblastic cell sources for reprogramming, such as astrocytes, olfactory ensheathing cells, peripheral blood cells, Müller glia, and more. We will examine benefits and obstructions for translation into therapeutics or disease modeling, as well as efficiency of the conversion. A summary of donor cells, induced neuron types, and methods of induction is also provided.
Highlights
Neurons are the primary functional unit of the brain and are a diverse, dynamic, and essential cell population of great importance to our study of cognitive function as well as therapeutic development for brain injury
The interest in developing direct reprogramming techniques can be attributed to advantages that arise from technical differences between induced pluripotent stem cell-derived induced neurons (iN) and directly reprogrammed iN derived from somatic cells
Directly reprogrammed neural precursor cells administered during the subacute phase of stroke demonstrated promising results for recovery in motor skills (Vonderwalde et al, 2020)
Summary
Neurons are the primary functional unit of the brain and are a diverse, dynamic, and essential cell population of great importance to our study of cognitive function as well as therapeutic development for brain injury. Direct reprogramming of somatic cells to various subtypes of induced neurons (iN) has great potential in the field of neuroscience research. This approach allows for disease modeling in neurons of human origin (even from the same patient) as well as the possibility for developing regenerative medicine therapies. The direct reprogramming approach can utilize endogenous patient cells as donors, removing the need for the complicated and expensive process of iPSC derivation, reprogramming, and engraftment. It reduces the risk of tumorigenesis/teratogenesis due to the lack of a pluripotent intermediate state and holds the potential of preserving the epigenetic memory
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