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Series GSE199372 Query DataSets for GSE199372
Status Public on Sep 21, 2023
Title scCNVseq Datasets Supporting Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
Organism Homo sapiens
Experiment type Other
Summary The translocation t(11;14) occurs in 20% of multiple myeloma (MM) patients and results in the upregulation of CCND1. Nearly two-thirds of t(11;14) MM cells are BCL2 primed and highly responsive to the oral BCL2 inhibitor venetoclax. While it is evident that this unique sensitivity to venetoclax depends on the BH3-proapoptotic protein priming of BCL2, the biology underlying t(11;14) MM dependency on BCL2 is poorly defined. Importantly, the epigenetic regulation of t(11;14) transcriptomes and its impact on gene regulation and clinical response to venetoclax remains elusive. In this study, by integrating ATACseq and RNAseq at the single-cell level in primary MM samples, we have defined the epigenetic regulome and transcriptome associated with t(11;14) MM. A "B cell-like" epigenetic signature was enriched in t(11;14) MM, confirming its phylogeny link to B cell rather than plasma cell biology. Of note, a loss of a "B cell-like" epigenetic signature with a gain of canonical plasma cell transcription factors was observed at the time of resistance to venetoclax. In addition, MCL1 and BCL2L1 copy number gains and structural rearrangements were linked to venetoclax resistance in t(11;14) MM patients. To date, this is the first study in which both scATAC-seq and scRNA-seq analysis are integrated into primary MM cells to obtain a deeper resolution of the epigenetic regulome and transcriptome associated with t(11;14) MM biology and venetoclax resistance.
 
Overall design Single-cell DNA sequencing (scDNA-seq)
Frozen cells were thawed at 37 °C, resuspended in RPMI 1640 medium (Gibco) and washed twice with cells being collected by centrifugation at 2000 rpm for 5 min. Viable CD138+ cells were counted and resuspended in a resuspension buffer at 1,000 cells per ul. Single-cell capture was then performed according to the manufacturer’s protocol, using Single Cell Bead Kit (10x Genomics, PN-1000057) and Chromium Chip C (PN-1000022) and D (PN-1000042) with a target capture of 1,000 cells. Quality control and quantification were performed using a KAPA Library Quantification qPCR kit (Roche, Basel, Switzerland) on a BioRad qPCR instrument. DNA libraries were prepared using Single Cell DNA Library & Gel Bead Kit (10x Genomics, PN-1000040) and sequenced on an Illumina NextSeq 500 sequencer with a high-output v2.5 300 cycle sequencing kit as per the standard Illumina protocols. After sequencing, bcl data were converted to fastq data files using the Illumina BCL2FASTQ utility. Samples were processed with CellRanger DNA v1.0.0 and downstream analyses were performed as indicated below.
 
Contributor(s) Leblay N, Ahn S, Tilmont R, Poorebrahim M, Maity R, Lee H, Barakat E, Alberge J, Sinha S, Jaffer A, Barwick BG, Boise LH, Bahlis NJ, Neri P
Citation(s) 37729611
Submission date Mar 24, 2022
Last update date Dec 01, 2023
Contact name Nizar Bahlis
E-mail(s) nbahlis@ucalgary.ca
Phone 403-220-2801
Organization name University of Calgary
Department Divisions of Hematology and Oncology
Street address 3330 Hospital Dr NW HMRB328
City Calgary
State/province Alberta
ZIP/Postal code T2N4N1
Country Canada
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (10)
GSM5971435 Patient_1217_PreTreatment CNV
GSM5971436 Patient_1389_Pre_Treatment CNV
GSM5971437 Patient_1404_Post_Treatment CNV
This SubSeries is part of SuperSeries:
GSE199373 Integrated Epigenetic and Transcriptional Single-Cell Analysis of t(11;14) Multiple Myeloma and Its BCL2 Dependency
Relations
BioProject PRJNA819463

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE199372_RAW.tar 7.3 Gb (http)(custom) TAR (of H5)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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