The single-cell transcriptional landscape of lung carcinoid tumors
The single-cell transcriptional landscape of lung carcinoid tumors
Abstract Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread while no consensus treatment exists for metastasized carcinoids. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the non-inflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.
Dziodzio Tomasz、Jurmeister Philipp、Horst David、Klauschen Frederick、Bl¨1thgen Nils、Wiederspahn Jennifer、Obermayer Benedikt、Pett Jan Patrick、Sers Christine、Morkel Markus、Beule Dieter、Elsner Aron、Falk Christine、Bischoff Philip、R¨1ckert Jens-Carsten、Neudecker Jens、Trinks Alexandra
Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||Charit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Surgery, Campus Charit¨| Mitte and Campus Virchow-KlinikumCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||Institute of Pathology, LMU MunichCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ)Charit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Institute of Pathology, LMU Munich||German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ)Charit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||IRI Life Sciences, Humboldt University of Berlin||German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ)Charit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||IRI Life Sciences, Humboldt University of BerlinBerlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin, Core Unit BioinformaticsBerlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin, Core Unit BioinformaticsCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ)Charit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin||German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ)Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin, Core Unit BioinformaticsCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Surgery, Campus Charit¨| Mitte and Campus Virchow-KlinikumInstitute of Transplant Immunology, Hannover Medical School||DZIF, German Center for Infectious Diseases, TTU-IICH Hannover-Braunschweig siteCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin BerlinCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Surgery, Campus Charit¨| Mitte and Campus Virchow-KlinikumCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Surgery, Campus Charit¨| Mitte and Campus Virchow-KlinikumCharit¨| - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Institute of Pathology||Berlin Institute of Health at Charit¨| - Universit?tsmedizin Berlin
肿瘤学细胞生物学分子生物学
Dziodzio Tomasz,Jurmeister Philipp,Horst David,Klauschen Frederick,Bl¨1thgen Nils,Wiederspahn Jennifer,Obermayer Benedikt,Pett Jan Patrick,Sers Christine,Morkel Markus,Beule Dieter,Elsner Aron,Falk Christine,Bischoff Philip,R¨1ckert Jens-Carsten,Neudecker Jens,Trinks Alexandra.The single-cell transcriptional landscape of lung carcinoid tumors[EB/OL].(2025-03-28)[2025-05-09].https://www.biorxiv.org/content/10.1101/2021.12.07.471416.点此复制
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