Suppr超能文献

体内神经胶质细胞向神经元的转化:陷阱与解决方案。

In vivo glia-to-neuron conversion: pitfalls and solutions.

机构信息

Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

出版信息

Dev Neurobiol. 2022 Jul;82(5):367-374. doi: 10.1002/dneu.22880. Epub 2022 May 23.

Abstract

Neuron loss and disruption of neural circuits are associated with many neurological conditions. A key question is how to rebuild neural circuits for functional improvements. In vivo glia-to-neuron (GtN) conversion emerges as a potential solution for regeneration-based therapeutics. This approach takes advantage of the regenerative ability of resident glial cells to produce new neurons through cell fate reprogramming. Significant progress has been made over the years in this emerging field. However, inappropriate analysis often leads to misleading conclusions that create confusion and hype. In this perspective, we point out the most salient pitfalls associated with some recent studies and provide solutions to prevent them in the future. The goal is to foster healthy development of this promising field and lay a solid cellular foundation for future regeneration-based medicine.

摘要

神经元丢失和神经回路的破坏与许多神经疾病有关。一个关键问题是如何重建神经回路以实现功能改善。体内神经胶质向神经元(GtN)转化为再生治疗提供了一种潜在的解决方案。这种方法利用了常驻神经胶质细胞的再生能力,通过细胞命运重编程产生新的神经元。近年来,在这个新兴领域取得了重大进展。然而,不恰当的分析往往会导致误导性的结论,造成混淆和炒作。在这篇观点文章中,我们指出了与最近一些研究相关的最突出的陷阱,并提供了未来防止这些陷阱的解决方案。目标是促进这一有前途的领域的健康发展,并为未来的再生医学奠定坚实的细胞基础。

相似文献

1
In vivo glia-to-neuron conversion: pitfalls and solutions.
Dev Neurobiol. 2022 Jul;82(5):367-374. doi: 10.1002/dneu.22880. Epub 2022 May 23.
2
New AAV tools fail to detect Neurod1-mediated neuronal conversion of Müller glia and astrocytes in vivo.
EBioMedicine. 2023 Apr;90:104531. doi: 10.1016/j.ebiom.2023.104531. Epub 2023 Mar 20.
3
Therapeutic Potential of PTBP1 Inhibition, If Any, Is Not Attributed to Glia-to-Neuron Conversion.
Annu Rev Neurosci. 2023 Jul 10;46:1-15. doi: 10.1146/annurev-neuro-092822-083410. Epub 2023 Feb 7.
4
Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina.
Cell Rep. 2022 Jun 14;39(11):110960. doi: 10.1016/j.celrep.2022.110960.
5
Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.
Cell Rep. 2022 Jun 14;39(11):110849. doi: 10.1016/j.celrep.2022.110849.
6
NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming.
Neuron. 2021 Dec 15;109(24):4094-4108.e5. doi: 10.1016/j.neuron.2021.11.008. Epub 2021 Dec 6.
7
Revisiting astrocyte to neuron conversion with lineage tracing in vivo.
Cell. 2021 Oct 14;184(21):5465-5481.e16. doi: 10.1016/j.cell.2021.09.005. Epub 2021 Sep 27.
8
In vivo glial trans-differentiation for neuronal replacement and functional recovery in central nervous system.
FEBS J. 2021 Aug;288(16):4773-4785. doi: 10.1111/febs.15681. Epub 2021 Jan 9.
10
Neurod1 mediates the reprogramming of NG2 glial into neurons in vitro.
Gene Expr Patterns. 2023 Mar;47:119305. doi: 10.1016/j.gep.2023.119305. Epub 2023 Jan 20.

引用本文的文献

1
Phosphorylation and DNA Damage Resolution Coordinate SOX2-Mediated Reprogramming in vivo.
bioRxiv. 2025 Jul 19:2025.07.15.664998. doi: 10.1101/2025.07.15.664998.
3
Changing genes, cells and networks to reprogram the brain after stroke.
Nat Neurosci. 2025 Jun;28(6):1130-1145. doi: 10.1038/s41593-025-01981-8. Epub 2025 Jun 2.
5
Sox2-overexpressing neural stem cells alleviate ventricular enlargement and neurological dysfunction in posthemorrhagic hydrocephalus.
Neural Regen Res. 2026 Feb 1;21(2):769-779. doi: 10.4103/NRR.NRR-D-24-01491. Epub 2025 Apr 30.
6
Recent progress of principal techniques used in the study of Müller glia reprogramming in mice.
Cell Regen. 2024 Dec 12;13(1):30. doi: 10.1186/s13619-024-00211-z.
9
NEUROD1: transcriptional and epigenetic regulator of human and mouse neuronal and endocrine cell lineage programs.
Front Cell Dev Biol. 2024 Jul 22;12:1435546. doi: 10.3389/fcell.2024.1435546. eCollection 2024.

本文引用的文献

2
A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum.
Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2107339119. doi: 10.1073/pnas.2107339119. Epub 2022 Mar 7.
3
Reprogramming cellular identity in vivo.
Development. 2022 Feb 15;149(4). doi: 10.1242/dev.200433. Epub 2022 Feb 23.
4
Limited astrocyte-to-neuron conversion in the mouse brain using NeuroD1 overexpression.
Mol Ther. 2022 Mar 2;30(3):982-986. doi: 10.1016/j.ymthe.2022.01.028. Epub 2022 Feb 4.
5
Lineage tracing: The gold standard to claim direct reprogramming in vivo.
Mol Ther. 2022 Mar 2;30(3):988-989. doi: 10.1016/j.ymthe.2022.01.029. Epub 2022 Feb 4.
6
Reply to In vivo confusion over in vivo conversion.
Mol Ther. 2022 Mar 2;30(3):986-987. doi: 10.1016/j.ymthe.2022.01.027. Epub 2022 Feb 1.
7
NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming.
Neuron. 2021 Dec 15;109(24):4094-4108.e5. doi: 10.1016/j.neuron.2021.11.008. Epub 2021 Dec 6.
8
Neuroregenerative gene therapy to treat temporal lobe epilepsy in a rat model.
Prog Neurobiol. 2022 Jan;208:102198. doi: 10.1016/j.pneurobio.2021.102198. Epub 2021 Nov 28.
10
cAAVe phaenomena: Beware of appearances!
Cell. 2021 Oct 14;184(21):5303-5305. doi: 10.1016/j.cell.2021.09.027.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验