Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most frequent and aggressive pancreatic tumor characterized by high metastatic risk and special tumor microenvironment. To comprehensively delineate the complex intra-tumoral heterogeneity and the underlying mechanism during metastatic lesions...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Qianhui Xu, Shaohuai Chen, Yuanbo Hu, Wen Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/689e994fd0f84f1ebf0b4b0d8b152230
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:689e994fd0f84f1ebf0b4b0d8b152230
record_format	dspace
spelling	oai:doaj.org-article:689e994fd0f84f1ebf0b4b0d8b1522302021-11-07T12:21:16ZSingle-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma10.1038/s41420-021-00663-12058-7716https://doaj.org/article/689e994fd0f84f1ebf0b4b0d8b1522302021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00663-1https://doaj.org/toc/2058-7716Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most frequent and aggressive pancreatic tumor characterized by high metastatic risk and special tumor microenvironment. To comprehensively delineate the complex intra-tumoral heterogeneity and the underlying mechanism during metastatic lesions malignant progression, single-cell RNA sequencing (scRNA-seq) was employed. PCA and TSNE were used for dimensionality reduction analysis and cell clustering. Find All Markers function was used to calculate differential genes in each cluster, and Do Heatmap function was used to plot the distribution of differential genes in each cluster. GSVA was employed to assign pathway activity estimates to individual cells. Lineage trajectory progression was inferred by monocle. CNV status was inferred to compare the heterogeneity among patients and subtypes by infercnv. Ligand-receptor interactions were identified by CellPhoneDB, and regulons network of cells was analyzed by SCENIC. Through RNA-sequencing of 6236 individual cells from 5 liver metastatic PDAC lesions, 10 major cell clusters are identified by using unbiased clustering analysis of expression profiling and well-known cell markers. Cells with high CNV level were considered as malignant cells and pathway analyses were carried out to highlight intratumor heterogeneity in PDAC. Pseudotime trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. The complex cellular communication suggested potential immunotherapeutic targets in PDAC. Regulon network identified multiple candidates for promising cell-specific transcriptional factors. Finally, metastatic-related genes expression levels and signaling pathways were validated in bulk RNA Sequencing data. This study contributed a comprehensive single-cell transcriptome atlas and contributed into novel insight of intratumor heterogeneity and molecular mechanism in metastatic PDAC.Qianhui XuShaohuai ChenYuanbo HuWen HuangNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Qianhui Xu Shaohuai Chen Yuanbo Hu Wen Huang Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
description	Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most frequent and aggressive pancreatic tumor characterized by high metastatic risk and special tumor microenvironment. To comprehensively delineate the complex intra-tumoral heterogeneity and the underlying mechanism during metastatic lesions malignant progression, single-cell RNA sequencing (scRNA-seq) was employed. PCA and TSNE were used for dimensionality reduction analysis and cell clustering. Find All Markers function was used to calculate differential genes in each cluster, and Do Heatmap function was used to plot the distribution of differential genes in each cluster. GSVA was employed to assign pathway activity estimates to individual cells. Lineage trajectory progression was inferred by monocle. CNV status was inferred to compare the heterogeneity among patients and subtypes by infercnv. Ligand-receptor interactions were identified by CellPhoneDB, and regulons network of cells was analyzed by SCENIC. Through RNA-sequencing of 6236 individual cells from 5 liver metastatic PDAC lesions, 10 major cell clusters are identified by using unbiased clustering analysis of expression profiling and well-known cell markers. Cells with high CNV level were considered as malignant cells and pathway analyses were carried out to highlight intratumor heterogeneity in PDAC. Pseudotime trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. The complex cellular communication suggested potential immunotherapeutic targets in PDAC. Regulon network identified multiple candidates for promising cell-specific transcriptional factors. Finally, metastatic-related genes expression levels and signaling pathways were validated in bulk RNA Sequencing data. This study contributed a comprehensive single-cell transcriptome atlas and contributed into novel insight of intratumor heterogeneity and molecular mechanism in metastatic PDAC.
format	article
author	Qianhui Xu Shaohuai Chen Yuanbo Hu Wen Huang
author_facet	Qianhui Xu Shaohuai Chen Yuanbo Hu Wen Huang
author_sort	Qianhui Xu
title	Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
title_short	Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
title_full	Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
title_fullStr	Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
title_full_unstemmed	Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
title_sort	single-cell rna transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/689e994fd0f84f1ebf0b4b0d8b152230
work_keys_str_mv	AT qianhuixu singlecellrnatranscriptomerevealstheintratumoralheterogeneityandregulatorsunderlyingtumorprogressioninmetastaticpancreaticductaladenocarcinoma AT shaohuaichen singlecellrnatranscriptomerevealstheintratumoralheterogeneityandregulatorsunderlyingtumorprogressioninmetastaticpancreaticductaladenocarcinoma AT yuanbohu singlecellrnatranscriptomerevealstheintratumoralheterogeneityandregulatorsunderlyingtumorprogressioninmetastaticpancreaticductaladenocarcinoma AT wenhuang singlecellrnatranscriptomerevealstheintratumoralheterogeneityandregulatorsunderlyingtumorprogressioninmetastaticpancreaticductaladenocarcinoma
_version_	1718443491440197632

Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma

Ejemplares similares