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Series GSE79874 Query DataSets for GSE79874
Status Public on Feb 20, 2018
Title Integrative analysis of 3D nucleome and chromatin accessibility reveals a chromatin barrier established for T-lineage commitment during early T cell development [ChIP-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Hematopoiesis consists of step-wise commitment of multiple distinct intermediate differentiation stages before mature blood cells are generated1,2. Early progenitor cells have multiple cell fate potentials and retain plasticity to differentiate to alternative lineages, while later stages are fully committed to certain cell lineages and rarely alter their fates3,4. Although extensive studies have been performed on regulatory pathways in mature blood cells5-8, few have examined chromatin re-organization underlying the transcription programs in early progenitors of hematopoiesis. In particular, what roles chromatin organization plays in the cell fate commitment during the differentiation of early hematopoietic progenitor cells remains unclear. Here, we carried out an integrative analysis of 3D nucleome, chromatin accessibility and gene expression during early T cell development from hematopoietic stem cells (HSC) to CD4/CD8 double positive (DP) T cells. Analysis of these data sets revealed extensive A/B compartment flips and dynamic changes of chromatin accessibility at regulatory regions including promoters and enhancers during the development process. Remarkably, both the compartment flip and changes in chromatin accessibility display a monotonic pattern. While gradual and progressive changes in chromatin re-organization was observed at most development stages, an abrupt and striking genome-wide change in A/B compartment structure and chromatin accessibility occurred during the transition from double negative stage 2 (DN2) to DN3, which was accompanied with the loss of cell fate plasticity of DN3 to differentiate to alternative lineages, suggesting that a chromatin barrier is established at the DN3 stage to lock the cells in the T cell fate. The binding of PU.1, a key factor for the fate choice of early progenitor cells, and BCL11B, critically required for T cell commitment at late stages, was associated with increased long-distance interaction and chromatin accessibility and may coordinately contribute to the establishment of the 3D nucleome structure required for the lineage differentiation and commitment.
 
Overall design To understand the contribution of chromatin interaction landscape to early development stages of hematopoesis, we generated genome-wide profiles of chromatin interaction (with an improved HiC protocal), chromatin accessibility (with scDNase-Seq) and gene expression (with RNA-Seq) from hematopoietic stem cells (HSC) and its immediate progeny (MPP) to common lymphocyte progenitor cells (CLP), early T progenitor cells (ETP or DN1), double negative stage 2 (DN2), DN3, DN4 and double positive (DP) cells.
 
Contributor(s) Gangqing H, Kairong C, Difeng F, Satoshi H, Xun W, Jingfang Z, Rothenberg EV, Keji Z
Citation(s) 29466755
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 AI083514 Bcl11b in early T cell development CALIFORNIA INSTITUTE OF TECHNOLOGY ELLEN V. ROTHENBERG
Submission date Apr 04, 2016
Last update date May 15, 2019
Contact name Satoshi Hirose
E-mail(s) hirose@caltech.edu
Phone 626-395-4915
Organization name California Institute of Technology
Department Biology and Bioengineering
Lab Rothenberg
Street address 1200 E. California
City Pasadena
State/province CA
ZIP/Postal code 91125
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM2107743 Bcl11b ChIP on thymoctes fixed with EGS and formaldehyde
GSM2107744 input DNA for Bcl11b ChIP on thymoctes fixed with EGS and formaldehyde
GSM2107745 Bcl11b ChIP on thymoctes fixed with formaldehyde #1
This SubSeries is part of SuperSeries:
GSE79875 Integrative analysis of 3D nucleome and chromatin accessibility reveals a chromatin barrier established for T-lineage commitment during early T cell development
Relations
BioProject PRJNA317302
SRA SRP072826

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Supplementary file Size Download File type/resource
GSE79874_RAW.tar 1.4 Gb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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