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Status |
Public on May 10, 2019 |
Title |
Single-cell lymphocyte heterogeneity inadvanced Cutaneous T-Cell Lymphoma skin tumors |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Purpose: The heterogeneity of tumor cells presents a major challenge to cancer diagnosis and therapy. Cutaneous T cell lymphomas (CTCL) are a group of T lymphocyte malignanciesthat primarily affect skin. Lack of highly specific markers for malignant lymphocytes prevents early diagnosis, while only limited treatment options are available for patients with advanced-stage CTCL.Droplet-basedsingle-cell transcriptome analysis of CTCL skin biopsiesopens avenues for dissecting patient-specificT lymphocyte heterogeneity, providing a basis for identifying specific markers for diagnosis and cure of CTCL. Experimental Design: Single-cell RNA-sequencing was performed by Droplet-based sequencing (10X Genomics), focusing on 14,056 CD3+lymphocytes (448 cells from normal and 13,608 cells from CTCL skin samples) from skin biopsies of 5 patients with advanced-stage CTCL and 4 healthy donors.Protein expression of identified genes was validated in advanced-stage CTCL skin tumors byimmunohistochemistry and confocal immunofluorescence microscopy. Results: Our analysis revealed a large inter- and intra-tumor gene expression heterogeneity in the T lymphocyte subset, as well as a common gene expression signature in highly proliferating lymphocytes that was validated in multiple advanced-stage skin tumors. In addition, we established the immunological state of reactive lymphocytes and found heterogeneity in effector and exhaution programs across patient samples. Conclusions: Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving anunprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, withimportant implications for diagnosis and personalized disease treatment.
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Overall design |
5 CTCL samples were analyzed and 4 normal controls were analyzed.
***Raw data will be submitted to dbGaP***
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Contributor(s) |
Gaydosik AM, Tabib T, Gerskin LJ, Bayan CY, Conway JF, Lafyatis R, FuschiottiĀ P |
Citation(s) |
31010835 |
Submission date |
Mar 19, 2019 |
Last update date |
Jun 14, 2022 |
Contact name |
Patrizia Fuschiotti |
E-mail(s) |
paf23@pitt.edu
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Organization name |
University of Pittsburgh
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Street address |
200 Lothrop St
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City |
Pittsburgh |
State/province |
PA |
ZIP/Postal code |
15261 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (9)
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Relations |
BioProject |
PRJNA528020 |
Supplementary file |
Size |
Download |
File type/resource |
GSE128531_RAW.tar |
93.2 Mb |
(http)(custom) |
TAR (of CSV) |
Raw data not provided for this record |
Processed data provided as supplementary file |
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