Enhanced P-TEFb activity compromises dentate gyrus neurogenesis in mice.
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- [1] § Methods › Single-cell sequencing, RNA-seq and bioinformatic analyses ↔ scRNA-seq.r, lines 1 to 39 · score 0.54 · RNA seq, Seurat, pre, matrix, mice, cell · Report a mismatch
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The authors' code
R · 227 lines · 7.7 KB · no license · 1 match
- #mouse ID8_P53KO_NACT
- #创建seurat对象
- library(Seurat)
- library(dplyr)
- library(ggplot2)
- library(patchwork)
- library(homologene)
- after<-Read10X("./ID8_P53KO_NACT_after/filtered_feature_bc_matrix/")
- after <- CreateSeuratObject(counts =after , project = "ID8_P53KO_NACT_after",min.cells = 3, min.features = 200)
- #质量控制
- after[["percent.mt"]] <- PercentageFeatureSet(after,pattern = "^mt-")
- preQC_after <- VlnPlot(after, features = c("nFeature_RNA", "nCount_RNA", "percent.mt"),
- ncol = 3,
- group.by = "orig.ident",
- pt.size = 0)
- ggsave("./after_preQC_1.pdf", preQC_after, width=7 ,height=6)
- #过滤低质量数据
- after <- subset(after, subset = nFeature_RNA > 200 & nFeature_RNA < 6000 & percent.mt < 15)
- preQC_after <- VlnPlot(after, features = c("nFeature_RNA", "nCount_RNA", "percent.mt"),
- ncol = 3,
- group.by = "orig.ident",
- pt.size = 0)
- after[["percent.rb"]] <- PercentageFeatureSet(after, pattern = "^RP[SL]")
- #去除线粒体基因
- mt.index <- grep(pattern = "^mt-", x = rownames(x = after@assays$RNA@counts), value = FALSE)
- after <- after[-mt.index,]
- #scale数据
- after <- NormalizeData(after,normalization.method = "LogNormalize", scale.factor = 10000)
- #特征选择
- after <- FindVariableFeatures(after, nfeatures = 4000, selected.method="vst")
- # 可视化高变基因
- var_plot <- VariableFeaturePlot(after)
- p3<-LabelPoints(plot = var_plot, points = head(VariableFeatures(after), repel = TRUE))
- ggsave("after_Variable_Genes.pdf", p3,width = 10)
- #缩放数据
- after <- ScaleData(after,verbose=FALSE)
- #细胞周期评分
- s.genes <- cc.genes$s.genes
- g2m.genes <- cc.genes$g2m.genes
- mouse.s.genes<-homologene(s.genes, inTax = 9606, outTax = 10090)
- mouse.g2m.genes<-homologene(g2m.genes, inTax = 9606, outTax = 10090)
- mouse.s.gene <- as.character(mouse.s.genes[[2]])
- mouse.g2m.gene <- as.character(mouse.g2m.genes[[2]])
- after <- CellCycleScoring(after,
- s.features = mouse.s.gene,
- g2m.features = mouse.g2m.gene,
- set.ident = TRUE)
- # PCA降维
- after <- RunPCA(
- after,
- features = VariableFeatures(object = after),
- npcs = 50 # 计算前50个主成分
- )
- # 可视化PCA结果
- p1<-DimPlot(after, reduction = "pca")
- ggsave("./after_pca_1.pdf",p1, width=7 ,height=6)
- p2<-ElbowPlot(after, ndims = 50) # 选择主成分数量(拐点位置)
- ggsave("./after_Eblowplot_1.pdf", p2, width=7 ,height=6)
- #聚类分析
- # 确定主成分数(通常10-30)
- pca_dims <- 1:30 # 根据ElbowPlot调整
- # 构建KNN图
- after <- FindNeighbors(after, dims = pca_dims)
- # 聚类(分辨率越高,簇越多)
- after <- FindClusters(
- after,
- resolution = 0.7 # 通常0.4-1.2(小样本用低值)
- )
- # 非线性降维 (UMAP/t-SNE)
- after <- RunUMAP(after, dims = pca_dims)
- after <- RunTSNE(after, dims = pca_dims)
- # 可视化聚类结果
- umap_plot <- DimPlot(after, reduction = "umap", label = TRUE)
- tsne_plot <- DimPlot(after, reduction = "tsne", label = TRUE)
- combined_plot <- umap_plot + tsne_plot
- ggsave("after_Clustering_UMAP_TSNE.pdf", combined_plot, width = 14)
- # ----------------------
- # 步骤7: 差异表达基因(标记基因)
- # ----------------------
- # 寻找每个簇的标记基因
- markers <- FindAllMarkers(
- after,
- only.pos = TRUE, # 只保留阳性标记
- min.pct = 0.25, # 基因在至少25%的簇细胞中表达
- logfc.threshold = 0.25
- )
- write.table(markers,file="./after_significant_marker_genes.txt",quote=F,sep="\t",col.names=FALSE)
- # 提取每个簇的前5标记基因
- top_markers <- markers %>%
- group_by(cluster) %>%
- slice_max(n = 5, order_by = avg_log2FC)
- # 可视化标记基因表达
- heatmap_plot <- DoHeatmap(
- after,
- features = top_markers$gene
- )
- ggsave("after_Marker_Heatmap.pdf", heatmap_plot, width = 12)
- saveRDS(after, file = "./01_ID8_p53KO_NACT_after_del_mt.RDS")
- #merge
- sampleList <- list(before,after)
- merge <- FindIntegrationAnchors(object.list = sampleList, dims = 1:50)
- merge <- IntegrateData(anchorset = merge, dims = 1:50)
- saveRDS(merge, file = "./merge/01_merge_mt_del.RDS")
- DefaultAssay(merge) <- "integrated"
- merge <- SCTransform(merge, variable.features.n=4000)
- merge <- RunPCA(merge, npcs = 50, verbose = FALSE)
- merge <- RunHarmony(merge,group.by.vars='orig.ident',dims=1:50,assay='SCT')
- merge <- FindNeighbors(merge, reduction = "harmony", dims = 1:30)
- merge <- FindClusters(merge, resolution = 0.5,algorithm=1)
- merge <- RunUMAP(merge, reduction = "harmony", dims = 1:30,assay='SCT')
- p1 <- DimPlot(merge, reduction = "umap", label = TRUE, repel = TRUE)
- p2 <- DimPlot(merge, reduction = "umap", group.by = "orig.ident",label=TRUE)
- write.table(merge$seurat_clusters,file="./all_merge_umapCluster.txt",quote=F,sep="\t",col.names=FALSE)
- ggsave("./01_merge_umap.pdf", p1, width=12 ,height=10)
- ggsave("./01_merge_umap_group.pdf", p2, width=12 ,height=10)
- saveRDS(merge, file = "./01_merge_mt_del_processed.RDS")
- #Cell Annotation
- marker_genes <- list(
- Astrocytes = c("Sox9", "Etv4","Sall3","Grin2c","Kcng4"),
- RG_like=c("Tfap2c", "Hopx","Rhcg","Vnn1","Wnt8b"),
- nIPC=c("Mxd3","Ascl1","Neurog2","Rfc4","Lockd"),
- Neuroblast1=c("Eomes","Neurod4","Slc17a6","Mpped1","Calb2"),
- Neuroblast2=c("Sox11","Bhlhe22","Neurod2","Gal","Igfbpl1"))
- merge <- AddModuleScore(merge, features = marker_genes, name = "ModuleScore")
- cluster_annotations <- [email hidden] %>%
- group_by(seurat_clusters) %>%
- summarize(across(starts_with("ModuleScore"), mean))
- predicted_cell_types <- cluster_annotations %>%
- rowwise() %>%
- mutate(predicted_type = names(marker_genes)[which.max(c_across(starts_with("ModuleScore")))])
- # 将预测的类型加入到Seurat对象的元数据中
- [email hidden]$predicted_type <- factor([email hidden]$seurat_clusters,
- levels = cluster_annotations$seurat_clusters,
- labels = predicted_cell_types$predicted_type)
- p1 <- DimPlot(merge, reduction = "umap", label = TRUE, repel = TRUE)
- p2 <- DimPlot(merge, reduction = "umap", group.by = "predicted_type",label=TRUE)
- DimPlot(merge, group.by = "predicted_type", label = TRUE, repel = TRUE) + NoLegend()
- write.table(merge$seurat_clusters,file="merge_umapCluster.txt",quote=F,sep="\t",col.names=FALSE)
- ggsave("merge_umap_predict_celltype.pdf", p1, width=12 ,height=10)
- ggsave("merge_umap_predict_celltype_group.pdf", p2, width=12 ,height=10)
- #执行差异表达分析
- # 获取所有细胞群体
- clusters <- unique(merge$manual_annotation)
- # 定义组别
- comparisons <- list(
- c("p7_l7_nestin", "p7_l7_wt"),
- c("p7_l7_nestin", "p7_l7_emxt"),
- c( "p7_l7_emxt", "p7_l7_wt")
- )
- # 存储结果
- results_list <- list()
- for (comparison in comparisons) {
- group1 <- comparison[1]
- group2 <- comparison[2]
- for (cluster in clusters) {
- # 选择当前群体的细胞
- cluster_cells <- WhichCells(merge, expression = manual_annotation == cluster)
- # 进行差异表达分析
- degs <- FindMarkers(
- object = merge,
- ident.1 = group1,
- ident.2 = group2,
- cells = cluster_cells,
- group.by = "orig.ident", min.pct=0.1,logfc.threshold=0.25, only.pos=F
- )
- # 存储结果,命名格式为: "群体_比较组1_vs_比较组2"
- results_list[[paste(cluster, group1, "vs", group2, sep = "_")]] <- degs
- }
- }
- 保存结果为CSV文件
- 将每个比较的结果保存为CSV文件。
- for (name in names(results_list)) {
- output_file <- paste0(name, "_DEGs.csv")
- write.csv(results_list[[name]], file = output_file, row.names = TRUE)
- }
scRNA-seq.r at commit 4a63c0d, no license · at the source
Overview
- Departments of Obstetrics & Gynecology and Pediatrics, Cancer Center, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Sichuan University,Chengdu, China
- Department of Medical Genetics, Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University,Chengdu, China
Abstract
Enhanced P-TEFb activity is thought to promote cell proliferation by increasing the transcriptional output of RNA polymerase II. The 7SK snRNP complex, which contains LARP7 and HEXIM1, sequesters and inhibits most cellular P-TEFb to prevent premature transcription elongation. Paradoxically, instead of exerting overgrowth effects, biallelic inactivation of LARP7 is linked to Alazami syndrome, a human neurodevelopmental disorder characterized by growth restriction and cognitive impairment. Here, we report that conditional ablation of either Larp7 or Hexim1 in the murine brain reduces the size and impairs the function of the hippocampal dentate gyrus during the neonatal period. Functional analyses reveal that increased P-TEFb activity enhances self-renewal transcriptional programs in transit-amplifying neuronal progenitor cells to limit neurogenesis in developing dentate gyri. These results demonstrate that dysregulated subtissular stem cell dynamics can reconcile increased P-TEFb activity with reduced organ growth, and suggest a translational opportunity for repurposing P-TEFb inhibitors to treat medical conditions affecting dentate gyrus size and function.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 1 match between paragraphs and lines of code.
ketone08/Larp7_KO_mouse
4a63c0da8eafd9ca97d365fe26c2539ce3a871a3, 23 June 2025Availability: 1 check, the latest on 30 September 2026: the link answers
- 30 September 2026: the link answers
5 files
- bubble_plot _intetrest_gene.r, R, 65 lines
- nIPC_Hexim_expression of GSE104323.r, R, 97 lines
- scRNA-seq.r, R, 227 lines, 1 match
- violin_plot_nCount_nFeat
ure_S_G2M.r , R, 36 lines - README.md, Text, 6 lines
The paper's code and data availability statement is in the Data section.
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Data
Datasets cited
- geo:GSE300207, at NCBI GEO; found in “Data availability”
Other data links
- ebi.ac.uk/
biostudies/ , EMBL-EBI; found in the notessourcedata
Data availability
The sequencing data produced in this study have been deposited in Gene Expression Omnibus (GEO) repository under the accession number GSE300207 (https://
The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_103
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 8 keywords, 10 MeSH terms, 3 funders, 80 references.
Cite
This paper
Fang, Y., Qiu, T., Wang, P., Bai, S., Wang, M., Yang, C., Wang, Y., Zhang, P., Wang, H., Liu, S., Xiao, X., & Li, Q. (2026). Enhanced P-TEFb activity compromises dentate gyrus neurogenesis in mice. The EMBO journal, 45(9), 3102-3123. https://
BibTeX
@article{fang2026enhance
author = {Fang, Yin and Qiu, Tong and Wang, Ping and Bai, Shujun and Wang, Min and Yang, Chao and Wang, Yan and Zhang, Peixuan and Wang, He and Liu, Shanling and Xiao, Xue and Li, Qintong},
title = {{Enhanced P-TEFb activity compromises dentate gyrus neurogenesis in mice}},
journal = {The EMBO journal},
year = {2026},
month = mar,
volume = {45},
number = {9},
pages = {3102--3123},
publisher = {Nature Publishing Group},
issn = {0261-4189},
doi = {10.1038/
url = {https://
pmid = {41872527},
pmcid = {PMC13144724}
}
RIS
TY - JOUR
AU - Fang, Yin
AU - Qiu, Tong
AU - Wang, Ping
AU - Bai, Shujun
AU - Wang, Min
AU - Yang, Chao
AU - Wang, Yan
AU - Zhang, Peixuan
AU - Wang, He
AU - Liu, Shanling
AU - Xiao, Xue
AU - Li, Qintong
TI - Enhanced P-TEFb activity compromises dentate gyrus neurogenesis in mice
T2 - The EMBO journal
J2 - EMBO J
PY - 2026
DA - 2026/
VL - 45
IS - 9
SP - 3102
EP - 3123
SN - 0261-4189
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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