Cited by 329Neurogenesis and neuroplasticity mechanismsPluripotent Stem Cells ResearchDevelopmental Biology and Gene Regulation

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Revisiting astrocyte to neuron conversion with lineage tracing in vivo

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Wang, Lei-Lei, Serrano, Carolina, Zhong, Xiaoling, Ma, Shuaipeng, Zou, Yuhua, Zhang, Chun-Li·2021·Cell

DOI 10.1016/j.cell.2021.09.005PMC PMC8526404

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Abstract

In vivo cell fate conversions have emerged as potential regeneration-based therapeutics for injury and disease. Recent studies reported that ectopic expression or knockdown of certain factors can convert resident astrocytes into functional neurons with high efficiency, region specificity, and precise connectivity. However, using stringent lineage tracing in the mouse brain, we show that the presumed astrocyte-converted neurons are actually endogenous neurons. AAV-mediated co-expression of NEUROD1 and a reporter specifically and efficiently induces reporter-labeled neurons. However, these neurons cannot be traced retrospectively to quiescent or reactive astrocytes using lineage-mapping strategies. Instead, through a retrograde labeling approach, our results reveal that endogenous neurons are the source for these viral-reporter-labeled neurons. Similarly, despite efficient knockdown of PTBP1 in vivo, genetically traced resident astrocytes were not converted into neurons. Together, our results highlight the requirement of lineage-tracing strategies, which should be broadly applied to studies of cell fate conversions in vivo.

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Authors: Wang, L.-L., Serrano, C., Zhong, X., Ma, S., Zou, Y., & Zhang, C.-L.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Wang, Lei-Lei
Zhang, Chun-Li
ORCID: Serrano, Carolina
Zhong, Xiaoling
Ma, Shuaipeng
Zhang, Chun-Li
Venue: Cell
Publisher: Elsevier BV
Published: 2021-10
Volume: 184
Issue: 21
Pages: 5465-5481.e16
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2021.09.005
PMC: PMC8526404
OpenAlex: W3203538421
Cited by: 329
References: 65
Citations by year: 2026: 30 · 2025: 60 · 2024: 74 · 2023: 68 · 2022: 73 · 2021: 21
FWCI: 21.49
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Welch Foundation (I-1724)
National Institutes of Health (NS099073, NS117065, NS111776, NS092616, NS088095)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: astrocyte-to-neuron conversion, lineage tracing, retrograde tracing, NeuroD1, PTBP1, reactive astrocytes, cell fate conversion, brain regeneration, mouse brain
MeSH terms: Dependovirus, Animals, Astrocytes, Brain, Brain Injuries, Cell Differentiation, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Promoter Regions, Genetic, Transcription Factors, Down-Regulation, Genes, Reporter, Homeodomain Proteins, Cell Lineage, Integrases, Heterogeneous-Nuclear Ribonucleoproteins, Polypyrimidine Tract-Binding Protein, Cell Line, Tumor, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Cellular Reprogramming

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Revisiting astrocyte to neuron conversion with lineage tracing in vivo

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