| Autor: |
Seongryong Kim, Galam Leem, Junjeong Choi, Yongjun Koh, Suho Lee, Sang-Hee Nam, Jin Su Kim, Chan Hee Park, Ho Kyoung Hwang, Kyoung Il Min, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seung Woo Park, Si Young Song, Eui-Cheol Shin, Chang Moo Kang, Seungmin Bang, Jong-Eun Park |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Genome Medicine, Vol 16, Iss 1, Pp 1-18 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1756-994X |
| DOI: |
10.1186/s13073-024-01287-7 |
| Popis: |
Abstract Background Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. Graphical Abstract |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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