Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data

The tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring ce...

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Main Authors: Jahanzeb Saqib, Beomsu Park, Yunjung Jin, Junseo Seo, Jaewoo Mo, Junil Kim
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/14/11/2033
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author Jahanzeb Saqib
Beomsu Park
Yunjung Jin
Junseo Seo
Jaewoo Mo
Junil Kim
author_facet Jahanzeb Saqib
Beomsu Park
Yunjung Jin
Junseo Seo
Jaewoo Mo
Junil Kim
author_sort Jahanzeb Saqib
collection DOAJ
description The tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring cells. To address this challenge and comprehensively assess the gene activity in tissue samples, it is imperative to integrate scRNA-seq with spatial transcriptomics. In our previous study on physically interacting cell sequencing (PIC-seq), we demonstrated that gene expression in single cells is affected by neighboring cell information. In the present study, we proposed a strategy to identify niche-specific gene signatures by harmonizing scRNA-seq and spatial transcriptomic data. This approach was applied to the paired or matched scRNA-seq and Visium platform data of five cancer types: breast cancer, gastrointestinal stromal tumor, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, and ovarian cancer. We observed distinct gene signatures specific to cellular niches and their neighboring counterparts. Intriguingly, these niche-specific genes display considerable dissimilarity to cell type markers and exhibit unique functional attributes independent of the cancer types. Collectively, these results demonstrate the potential of this integrative approach for identifying novel marker genes and their spatial relationships.
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spelling doaj.art-d586257dd31e4cb481847aa6e870d7a92023-11-24T14:43:51ZengMDPI AGGenes2073-44252023-10-011411203310.3390/genes14112033Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics DataJahanzeb Saqib0Beomsu Park1Yunjung Jin2Junseo Seo3Jaewoo Mo4Junil Kim5School of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaSchool of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaSchool of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaSchool of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaSchool of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaSchool of Systems Biomedical Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of KoreaThe tumor microenvironment significantly affects the transcriptomic states of tumor cells. Single-cell RNA sequencing (scRNA-seq) helps elucidate the transcriptomes of individual cancer cells and their neighboring cells. However, cell dissociation results in the loss of information on neighboring cells. To address this challenge and comprehensively assess the gene activity in tissue samples, it is imperative to integrate scRNA-seq with spatial transcriptomics. In our previous study on physically interacting cell sequencing (PIC-seq), we demonstrated that gene expression in single cells is affected by neighboring cell information. In the present study, we proposed a strategy to identify niche-specific gene signatures by harmonizing scRNA-seq and spatial transcriptomic data. This approach was applied to the paired or matched scRNA-seq and Visium platform data of five cancer types: breast cancer, gastrointestinal stromal tumor, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, and ovarian cancer. We observed distinct gene signatures specific to cellular niches and their neighboring counterparts. Intriguingly, these niche-specific genes display considerable dissimilarity to cell type markers and exhibit unique functional attributes independent of the cancer types. Collectively, these results demonstrate the potential of this integrative approach for identifying novel marker genes and their spatial relationships.https://www.mdpi.com/2073-4425/14/11/2033single-cell RNA sequencingspatial transcriptomicstumor microenvironmentsdata integrationniche-specific genesspatial correlation
spellingShingle Jahanzeb Saqib
Beomsu Park
Yunjung Jin
Junseo Seo
Jaewoo Mo
Junil Kim
Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
Genes
single-cell RNA sequencing
spatial transcriptomics
tumor microenvironments
data integration
niche-specific genes
spatial correlation
title Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
title_full Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
title_fullStr Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
title_full_unstemmed Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
title_short Identification of Niche-Specific Gene Signatures between Malignant Tumor Microenvironments by Integrating Single Cell and Spatial Transcriptomics Data
title_sort identification of niche specific gene signatures between malignant tumor microenvironments by integrating single cell and spatial transcriptomics data
topic single-cell RNA sequencing
spatial transcriptomics
tumor microenvironments
data integration
niche-specific genes
spatial correlation
url https://www.mdpi.com/2073-4425/14/11/2033
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