EXPERIMENT_TITLE: GSM4409232: 121_HiC; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Leukemia blast cells were prepared by density-gradient centrifugation of bone marrow samples, and CD19-CD14-CD235-CD45+CD7+ cells were further purified by FACS analysis using anti-human antibodies for RNA-seq and Hi-C library preparations. Peripheral blood samples were obtained from four healthy donors under the approval of the ethics committee of Peking University. T cells were purified using the EasySepTM Direct Human T Cell Isolation Kit (StemCell Technology #19661). Hi-C was performed on one million cells/sample according to the BL-Hi-C protocol (PMID: 29158486 ). RNA libraries were prepared for sequencing using standard Illumina protocols. ATAC  was performed on 50,000 Loucy cells according to the Omni-ATAC protocol  (PMID:28846090) with TruePrep DNA Library Prep Kit V2 for Illumina® (Vazyme TD501)
STUDY_DESCRIPTOR_STUDY_ABSTRACT: The goals of this study are to determine whether alterations in the 3D genome organization are associated with the malignant transformation of T-ALL. We report integrated analyses of 3D genome alterations and differentially expressed genes (DEGs) in 18 newly diagnosed T-ALL patients and 4 healthy T cell controls. We found that 3D genome reorganization at the compartment, topologically associated domains (TAD), and loop levels in different subtypes of T-ALL. Alterations in the 3D genome were associated with nearly 45% of the upregulated genes in T-ALL. We also identified 34 novel translocations in the noncoding regions of the genome and 44 new loops formed between translocated chromosomes.  These translocations can activate the expression of oncogenic transcription factors including HOXA11-A13 by “cis” or “trans” reorganization of chromatin structure. Our analysis demonstrated that T-ALLs with HOXA cluster overexpression were heterogeneous clinical entities, and ectopic expressions of the HOXA11-A13 genes, but not other genes in the HOXA cluster, were associated with immature phenotypes and poor outcomes. Our findings highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL. Overall design: We conducted BL-Hi-C and RNA-seq using purified primary leukemic blasts from 18 newly diagnosed T-ALL patients, including 8 early T-cell precursors ALL (ETP ALL) and 10 non-ETP ALL, two clinical subtypes of T-ALL, as well as normal T cells from 4 healthy volunteers. Raw data and all the processed data were deposited on this GEO Series.All Raw sequence data were also provided at China Genomic Sequence Archive (GSA) (under accession HRA000113 https://bigd.big.ac.cn/gsa-human/browse/HRA000113). UCSC sessions: https://genome.ucsc.edu/s/ChenFengling/TALL
SAMPLE_TITLE: 121_HiC
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "bone marrow"}, {"TAG": "cell type", "VALUE": "primary leukemic blasts"}, {"TAG": "age", "VALUE": "14"}, {"TAG": "subtype", "VALUE": "nonETP"}]
Pool_Member_@attributes_sample_title: 121_HiC
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