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单细胞数据有助于剖析批量转录组数据中存在的细胞类型。

Single Cell Data Enables Dissecting Cell Types Present in Bulk Transcriptome Data.

作者信息

Wruck Wasco, Adjaye James

机构信息

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

EGA Institute for Women's Health, Zayed Centre for Research into Rare Diseases in Children (ZCR), University College London (UCL), London, UK.

出版信息

Stem Cells Dev. 2025 Jan;34(1-2):17-25. doi: 10.1089/scd.2024.0152. Epub 2024 Nov 29.

Abstract

The quality of organoid models can be assessed by single-cell-RNA-sequencing (scRNA-seq) but often only bulk transcriptome data is available. Here we present a pipeline for the analysis of scRNA-seq data and subsequent "deconvolution," which is a method for estimating cell type fractions in bulk transcriptome data based on expression profiles and cell types found in scRNA-seq data derived from biopsies. We applied this pipeline on bulk iPSC-derived kidney and brain organoid transcriptome data to identify cell types employing two scRNA-seq kidney datasets and one brain dataset. Relevant cells present in kidney (e.g., proximal tubules, distal convoluted tubules, and podocytes) and brain (e.g., neurons, astrocytes, oligodendrocytes, and microglia) with obligatory endothelial and immune-related cells were identified. We anticipate that this pipeline will also enable estimation of cell type fractions in organoids of other tissues.

摘要

类器官模型的质量可以通过单细胞RNA测序(scRNA-seq)进行评估,但通常只能获得批量转录组数据。在此,我们展示了一个用于分析scRNA-seq数据及后续“反卷积”的流程,“反卷积”是一种基于活检来源的scRNA-seq数据中的表达谱和细胞类型来估计批量转录组数据中细胞类型比例的方法。我们将此流程应用于诱导多能干细胞(iPSC)来源的肾脏和脑类器官转录组批量数据,使用两个scRNA-seq肾脏数据集和一个脑数据集来识别细胞类型。确定了肾脏中存在的相关细胞(如近端小管、远端曲管和足细胞)以及脑中的相关细胞(如神经元、星形胶质细胞、少突胶质细胞和小胶质细胞),还有必不可少的内皮细胞和免疫相关细胞。我们预计该流程还将能够估计其他组织类器官中的细胞类型比例。

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