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Series GSE85853 Query DataSets for GSE85853
Status Public on Apr 20, 2017
Title Chromatin accessibility landscape of cutaneous T cell lymphoma and dynamic response to HDAC inhibitors
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by Assay of Transposase-Accessible Chromatin (ATAC-seq). Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic vs. non-leukemic (host) CD4+ T cells in CTCL patients, vs. CD4+ T cells in healthy donors. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

Overall design We examined chromatin structure using ATAC-seq in purified human CD4+ T cells in 30 samples from 10 health donors and 81 samples from 14 patiets with cutaneous T cell leukemia (CTCL), treated with HDACi anti-cancer drugs, such as Vorinostat and Romidepsin. Each donor provided cells per time point via a single standard 5 ml blood draw, and CD4+ T cells were isolated applying RosetteSep Human CD4+ T Cell Enrichment Cocktail (Experimental Procedures). Because CTCL is typically characterized by a dominant CD4+ T cell clone bearing an unique T cell receptor, we purified CTCL leukemic cells from patients (defined by CD4+, CD26-, and T cell receptor V-beta clone+) vs. host CD4+ T-cell (defined by CD4+, CD26-, V-beta clone-) from the same patients by fluorescence activated cell sorting (FACS). Leukemic, host and bulk T cells were obtained from 10 out of 15 patients who had detectable V-beta clone, and only bulk T cells were obtained for the remaining 5 patients without detectable V-beta clone. Although number and proportion of leukemic and host cells varies depending on the stage and drug response of each individual, especially at a later stage of drug treatment, we were able to obtain at least 50,000 CD4+ T cells per sample.

Please note that the indicated 'Day' (in the sample title) for Normal donors means when the blood was drew. For example “Normal_Donor1_Day38_Rep2” means this sample was drew on day 38. Day for Patients means days after the first drug treatment. For example “BulkCTCL_Patient1366_Romi_Day28” means this is a Bulk cell sample from Patient 1366, who was treated with Romidepsin, and the blood was drew on Day 28 according to the first day of treatment, and on that day, the patient was also treated with the same drug.
Contributor(s) Qu K, Zaba LC, Giresi PG, Li R, Armstrong R, Greenleaf WJ, Kim YH, Chang HY
Citation(s) 28625481
Submission date Aug 19, 2016
Last update date May 15, 2019
Contact name Kun Qu
Organization name Stanford University
Department Dermatology
Lab Howard Chang
Street address 269 Campus Dr. CCSR 2150
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (126)
GSM2285569 Normal_Donor1_Day1_Rep1
GSM2285570 Normal_Donor1_Day1_Rep2
GSM2285571 Normal_Donor1_Day2_Rep1
BioProject PRJNA339552
SRA SRP082417

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Supplementary file Size Download File type/resource
GSE85853_AllPeaks.bed.gz 998.6 Kb (ftp)(http) BED
GSE85853_BulkCTCLPeaks.bed.gz 738.1 Kb (ftp)(http) BED
GSE85853_BulkStage3Peaks.bed.gz 656.7 Kb (ftp)(http) BED
GSE85853_HostPeaks.bed.gz 680.4 Kb (ftp)(http) BED
GSE85853_LeukemicPeaks.bed.gz 698.4 Kb (ftp)(http) BED
GSE85853_NormalPeaks.bed.gz 846.5 Kb (ftp)(http) BED
GSE85853_TcellSubtypePeaks.bed.gz 967.1 Kb (ftp)(http) BED
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