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References
Hoang, T. et al. Ptbp1 depletion does not induce astrocyte-to-neuron conversion. Nature https://doi.org/10.1038/s41586-023-06066-9 (2023).
Qian, H. et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 582, 550–556 (2020).
Wang, L.-L. et al. Revisiting astrocyte to neuron conversion with lineage tracing in vivo. Cell 184, 5465–5481 (2021).
Chen, W., Zheng, Q., Huang, Q., Ma, S. & Li, M. Repressing PTBP1 fails to convert reactive astrocytes to dopaminergic neurons in a 6-hydroxydopamine mouse model of Parkinson’s disease. eLife 11, e75636 (2022).
Shibayama, M. et al. Polypyrimidine tract‐binding protein is essential for early mouse development and embryonic stem cell proliferation. FEBS J. 276, 6658–6668 (2009).
Xue, Y. et al. Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells. Nat. Neurosci. 19, 807–815 (2016).
Lu, T. et al. REST and stress resistance in ageing and Alzheimer’s disease. Nature 507, 448–454 (2014).
Gao, Z. et al. The master negative regulator REST/NRSF controls adult neurogenesis by restraining the neurogenic program in quiescent stem cells. J. Neurosci. 31, 9772–9786 (2011).
El-Brolosy, M. A. & Stainier, D. Y. Genetic compensation: a phenomenon in search of mechanisms. PLoS Genet. 13, e1006780 (2017).
Boutz, P. L. et al. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 21, 1636–1652 (2007).
Xue, Y. et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 152, 82–96 (2013).
Zhang, X. et al. CellMarker: a manually curated resource of cell markers in human and mouse. Nucleic Acids Res. 47, D721–D728 (2019).
Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979–982 (2017).
Luecken, M. D. & Theis, F. J. Current best practices in single-cell RNA-seq analysis: a tutorial. Mol. Syst. Biol. 15, e8746 (2019).
McGinnis, C. S., Murrow, L. M. & Gartner, Z. J. DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 8, 329–337 (2019).
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Y.H. performed analysis of the scRNA-seq data. H.Q., J.H. and X.-D.F. wrote the Reply with input from J.H., Y.X., S.F.D. and W.C.M. Note that the author list is different from that in the original paper2 because we recruited the first author of the Reply, Y.H., to analyse the scRNA-seq data and omitted several collaborators whose work was not related to the subjects raised by Hoang et al.1.
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Extended data figures and tables
Extended Data Fig. 1 Quality control in analyzing the scRNA-seq data.
a,b,c, Violin plots of n-count_RNA, n-feature_RNA and Percent_mt (mitochondrial transcripts) distribution in cells from WT, heterozygous or homozygous Ptbp1 KO cortex (a), striatum (b) and substantia nigra (c). Center lines in boxplots are the median and box is the interquartile range (IQR). n = 13198, n = 14732, n = 17071 cells for WT, heterozygous and homozygous Ptbp1 KO cortex; n = 12145, n = 12175, n = 15710 cells for WT, heterozygous and homozygous Ptbp1 KO striatum; n = 5741, n = 4518, n = 2965 cells for WT, heterozygous and homozygous Ptbp1 KO substantia nigra. d,e,f, Expression of cell type-specific marker genes in each cluster defined from cortex (d), striatum (e) and substantia nigra (f) scRNA-seq data.
Extended Data Fig. 2 Reanalyzing the scRNA-seq data from striatum.
a, UMAP of cells from striatum of different genotypes (left). Colored clusters are annotated to different cell types based on an established panel of cell markers. Expression of top 10 marker genes in Cluster 10 was compared with other clusters (right). Red text: neuronal genes. b, Expression of GFP, Ptbp1, and Ptbp2 in individual cell clusters from WT (red); green: heterozygous (green), and homozygous (blue) Ptbp1 KO mice.
Extended Data Fig. 3 Reanalyzing the scRNA data from substantia nigra.
a, UMAP of cells from substantia nigra of different genotypes. b, Relative quantity of cells in different clusters (indicated at top). c, Expression of GFP, Ptbp1, and Ptbp2 in individual cell clusters from WT (red), heterozygous (green), and homozygous (blue) Ptbp1 KO mice. d, Expression of top 10 marker genes in Cluster 5, compared with other clusters (right). Green text: astrocytic genes, Red text: neuronal genes. e, Identification of potential doublets with DoubletFinder, showing that most cells in Cluster 5 are unlikely to be doublets.
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Hao, Y., Hu, J., Xue, Y. et al. Reply to: Ptbp1 deletion does not induce astrocyte-to-neuron conversion. Nature 618, E8–E13 (2023). https://doi.org/10.1038/s41586-023-06067-8
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DOI: https://doi.org/10.1038/s41586-023-06067-8
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