Direct Lineage Reprogramming for Brain Repair: Breakthroughs and Challenges
Injury to the human central nervous system (CNS) is devastating because our adult mammalian brain lacks intrinsic regenerative capacity to replace lost neurons and induce functional recovery. An emerging approach towards brain repair is to instruct fate conversion of brain-resident non-neuronal cell...
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Published in | Trends in molecular medicine Vol. 25; no. 10; pp. 897 - 914 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.10.2019
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Injury to the human central nervous system (CNS) is devastating because our adult mammalian brain lacks intrinsic regenerative capacity to replace lost neurons and induce functional recovery. An emerging approach towards brain repair is to instruct fate conversion of brain-resident non-neuronal cells into induced neurons (iNs) by direct lineage reprogramming. Considerable progress has been made in converting various source cell types of mouse and human origin into clinically relevant iNs. Recent achievements using transcriptomics and epigenetics have shed light on the molecular mechanisms underpinning neuronal reprogramming, while the potential capability of iNs in promoting functional recovery in pathological contexts has started to be evaluated. Although future challenges need to be overcome before clinical translation, lineage reprogramming holds promise for effective cell-replacement therapy in regenerative medicine.
Recent single-cell transcriptome profiling and epigenetic studies have shed light on reprogramming trajectories and molecular mechanisms underpinning neuronal conversion.A recent approach to replace lost neurons in the injured brain is to induce fate conversion of brain-resident non-neuronal cells into iNs by direct lineage reprogramming.Various source cell types, including murine astrocytes, NG2 glia, and microglia, can be converted into clinically relevant iNs of diverse phenotypes in vitro and in vivo, by forced expression of specific transcription factors or exposure to small molecules.Human astrocytes and pericytes can be reprogrammed into functional iNs, opening up avenues towards use of endogenous patient-specific cells towards repair in the human brain.Lineage reprogramming holds promise for future neuron replacement therapy in regenerative medicine. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 1471-4914 1471-499X |
DOI: | 10.1016/j.molmed.2019.06.006 |