Unknown,Transcriptomics,Genomics,Proteomics

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DNA Methylation data from early human B-cell development

ABSTRACT: A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res. 2012 Dec;40(22):11339-51. We examined DNA methylation and RNA expression status during early B-cell development by sorting multiple replicates of four separate stages of pre-B cells derived from normal human fetal bone marrow and applied high-dimension DNA methylation scanning and expression arrays. We identified a distinct development-dependent demethylation signature which has gene expression regulatory properties for pre-B cells, and provide a catalog reference for the epigenetic changes that occur in pre-B-cell leukemia and other B-cell-related diseases. Human fetal bone marrow was obtained, and using flow cytometry antibodies, four populations of B-cell developmental stages including stage 1 (S1; predominantly multipotent progenitors before lineage commitment and common lymphoid progenitors), stage II (S2; pre-B-I cells), stage 3 (S3; pre-B-II cells) and stage 4 cells (S4; immature B cells). For 8 indibiduals, DNAs and RNAs were isolated and the methylation and expression changes during early B-cell development were identified using the Illumina HumanMethylation450 Beadchip (Illumina) and GeneChip Human Gene 1.0 ST Array (Affymetrix).

ORGANISM(S): Homo sapiens

SUBMITTER: Seung-Tae Lee

PROVIDER: E-GEOD-45459 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.

Lee Seung-Tae ST Xiao Yuanyuan Y Muench Marcus O MO Xiao Jianqiao J Fomin Marina E ME Wiencke John K JK Zheng Shichun S Dou Xiaoqin X de Smith Adam A Chokkalingam Anand A Buffler Patricia P Ma Xiaomei X Wiemels Joseph L JL

Nucleic acids research 20121016 22

The epigenetic changes during B-cell development relevant to both normal function and hematologic malignancy are incompletely understood. We examined DNA methylation and RNA expression status during early B-cell development by sorting multiple replicates of four separate stages of pre-B cells derived from normal human fetal bone marrow and applied high-dimension DNA methylation scanning and expression arrays. Features of promoter and gene body DNA methylation were strongly correlated with RNA ex ...[more]

PMID: 23074194

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Project description:The main goal of the project is to develop a new generation of bioinformatics resources for the integrative analysis of multiple types of 'omics data. These resources include both novel statistical methodologies as well as user-friendly software implementations. STATegra methods address many aspects of the 'omics data integration problem such as the design of multi-omics experiments, integrative transcriptional and regulatory networks, integrative variable selection, data fusion, integration of public domain data, and integrative pathway analysis. To support method development STATegra uses a model biological system, namely the differentiation process of mouse pre-B-cells. The STATegra consortium generated data focused on a critical step in the differentiation of B lymphocytes, which are key components of the adaptive immune system. Transcription factors of the Ikaros family are central to the normal differentiation of B cell progenitors and their expression increases in response to developmental stage-specific signals to terminate the proliferation of B cell progenitors and to initiate their differentiation. In particular, a novel biological system that models the transition from the pre-BI stage to the pre-BII subsequent stage, where B cell progenitors undergo growth arrest and differentiation, was used. The approach involves a pre-B cell line, B3, and an inducible version of the Ikaros transcription factor, Ikaros-ERt2. Ikaros factors act to down-regulate genes that drive proliferation and to simultaneously up-regulate the expression of genes that promote the differentiation of B cell progenitors. Hence, in the B3 system, before induction of Ikaros, cells proliferate and their gene expression pattern is similar to proliferating B cell progenitors in vivo. Following Ikaros induction, B3 cells undergo gene expression changes that resemble those that occur in vivo during the transition from cycling to resting pre-B cells, followed by a marked reduction in cellular proliferation and by G1 arrest. On this system the consortium has created a high-quality data collection consisting of a replicated time course using seven different 'omics platforms: RNA-seq, miRNA-seq, ChIP-seq, DNase-seq, Methyl-seq, proteomics and metabolomics, which is used to assess and to validate STATegra methods. The STATegra experimental design consists of a 6 point time course that captures the differentiation of B3 cells containing Ikaros-ERt2 upon Ikaros induction within a 24 hr period. The process was sampled at 0, 2, 6, 12, 18, and 24 hrs respectively after Ikaros induction by Tamoxifen. As control, B3 cells transfected with an empty vector were treated and sampled in the same way as the inducible line. Eight different 'omic technologies were measured on this system: RNA-seq, miRNA-seq, DNase-seq, RRBS-seq, ChIP-seq, scRNA-seq, Proteomics and Metabolomics. Generally, three biological replicates were obtained per platform and were processed as independent batches. Metabolomics analysis was performed using 4 biological batches (7, 8, 9 and 10) and at times 0, 2, 6, 12, 18 and 24 hrs respectively. Each sample was analyzed using gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS).

Dataset Information

DNA Methylation data from early human B-cell development

Publications

A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.

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