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Series GSE151230 Query DataSets for GSE151230
Status Public on Feb 25, 2021
Title Gata2 loss alters epigenetic priming and gene expression profiles in early myeloid and lymphoid progenitors leading to cytopenias [ATAC-seq]
Organism Danio rerio
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Germline heterozygous mutations in GATA2 are associated with a syndrome characterized by cytopenias, atypical infections, and increased risk of hematologic malignancies. Due to embryonic lethality of Gata2-/- mice, the role of germline loss of GATA2 has not been studied in adult hematopoiesis. Here, we generated a zebrafish mutant of gata2b, which in adulthood recapitulated the myelomonocytopenia and B cell lymphopenia of GATA2 syndrome. Using single cell epigenetic and transcriptomic analyses, we showed that loss of gata2b alters chromosome accessibility and results in gene expression changes in both early myeloid and lymphoid progenitors. We found differentiation block with skewing away from the monocytic program in myeloid progenitors in gata2bko zebrafish. In lymphoid progenitors, gata2b loss led to increased lymphoid priming but with incomplete B cell lymphopoiesis. These results place GATA2 in critical junctions of lineage specification in adult hematopoiesis.
Overall design Two approaches of single cell ATAC sequencing were used on unsorted zebrafish kidney marrow cell from wildtype, gata2b heterozygous and gata2b homozygous mutants (exon 2 CRISPR mutants described in this paper). One approach was sci-ATAC sequencing (used for 1 wildtype and 1 gata2b homozygous knockout) and the other was 10x Genomics scATAC sequencing platform (3 wildtype, 2 gata2b heterozygous and 3 gata2b homozygous mutants). The zebrafish underwent cardiac bleeding to reduce amount of peripheral blood in the marrow samples. No other manipulation was performed on the marrow cells. Single nuclei were obtained by the protocol described in the manuscript.
Contributor(s) Avagyan S, Ma S, Yang S, Zon LI
Citation(s) 34170284
Submission date May 26, 2020
Last update date Jul 02, 2021
Contact name Leonard Zon
Organization name Boston Children's Hospital
Department Oncology/Hematology
Street address 1 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL24995 Illumina NovaSeq 6000 (Danio rerio)
Samples (9)
GSM4568898 sci-ATAC-seq_wildtype and ko
GSM4568899 ATAC-seq_wildtype 2
GSM4568900 ATAC-seq_wildtype 3
This SubSeries is part of SuperSeries:
GSE151232 Gata2 loss alters epigenetic priming and gene expression profiles in early myeloid and lymphoid progenitors leading to cytopenias
BioProject PRJNA635160
SRA SRP264837

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