Somatic genetic alterations predict hematological progression in GATA2 deficiency
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB55350 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We generated homozygous GATA2 knockout human embryonic stem cells (GATA2-/- hESCs) and analyzed their blood differentiation potential. Paritcularly at the hemogenic endothelium (HE) stage and hematopoietic progenitor cell (HPC) stage. Our result revealed that GATA2-/- hESCs displayed attenuated generation of CD34+CD43+ HPCs, due to the impairment of endothelial to hematopoietic transition (EHT). However, GATA2-/- hESCs retained the potential to generate erythroblasts, macrophages, but never granulocytes. Through RNA-Seq and further rescue experiment, we further identified that SPI1 was responsible for the defect of GATA2-/- hESCs in generation of CD34+CD43+ HPCs and granulocytes.
2017-02-09 | GSE69797 | GEO
Project description:The Gata2 transcription factor is a pivotal regulator of hematopoietic stem cell (HSC) development and maintenance. Gata2 functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) to affect hematopoietic cluster, HPC and HSC formation. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study we generate a Gata2 Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. Gata2Venus- HPCs 1 replicate, Gata2Venus+ HPCs 1 replicate
2015-12-22 | E-GEOD-76254 | biostudies-arrayexpress
Project description:The Gata2 transcription factor is a pivotal regulator of hematopoietic stem cell (HSC) development and maintenance. Gata2 functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) to affect hematopoietic cluster, HPC and HSC formation. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study we generate a Gata2 Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells.
2015-12-22 | GSE76254 | GEO
Project description:Cell fate is established through coordinated gene expression programs in individual cells. Regulatory networks that include the Gata2 transcription factor play central roles in hematopoietic fate establishment. Whereas Gata2 is essential to the embryonic development and function of hematopoietic stem cells that form the adult hierarchy, little is known of the in vivo expression dynamics of Gata2 in single cells. Here we examine Gata2 expression in single aortic cells as they establish hematopoietic fate in Gata2Venus mouse embryos. Time-lapse imaging reveals rapid pulsatile level changes in Gata2 reporter expression in cells undergoing endothelial-to-hematopoietic-transition. Moreover, Gata2 reporter pulsatile expression is dramatically altered in Gata2+/- aortic cells, which undergo fewer transitions and are reduced in hematopoietic potential. Our novel finding of dynamic pulsatile expression of Gata2 suggests a highly unstable genetic state in single cells concomitant with their transition to hematopoietic fate. This reinforces the notion that threshold levels of Gata2 influence fate establishment and has implications for transcription factor-related hematologic dysfunctions.
2017-10-25 | GSE106072 | GEO
Project description:RNA-seq data of primary hematopoietic progenitor cells from -77 knockout mice which expressing Gata2 and controls
2020-06-18 | GSE133606 | GEO
Project description:The majority (72%) of adolescents with myelodysplastic syndrome and monosomy 7 carry an underlying GATA2 deficiency. Nowadays, chemotherapy and allogenic hematopoietic stem cell transplantation (HSCT) are the only cure, pointing out the urgent need to develop reliable predictive tools. Familial cases carrying the same mutation in the GATA2 gene develop the disease at different age. The trigger of the disease is still unknown. Therefore, it is needed to understand the genetic mechanisms (mutations) and epigenetic mechanism, such as, DNA methylation, a cellular mechanism to control gene expression. Abnormal DNA methylation has been linked to several adverse outcomes, including human diseases. In this study, we deeply characterized 20 Spanish GATA2 deficient patients; study the presence of secondary mutations, clinical phenotype and DNA methylation. We have found that the most frequent secondary mutations are in STAG2 and ASXL1 genes, detected in 30% and 20% of the patients, respectively, a similar ratio has been described in a bigger cohort, showing that our 20-patient cohort is representative of the GATA2 deficiency scenario. For the first time, we found a specific hypermethylated signature in GATA2 patients, opening a novel point of view in the GATA2-patient diagnostic and facilitating the risk estimation of themselves. Furthermore, whether the methylation profiling is accurate enough, it will be useful to predict the onset of the disease progression.
2023-06-30 | E-MTAB-12551 | biostudies-arrayexpress
Project description:Background and Purpose: Constitutional GATA2 deficiency caused by heterozygous germline GATA2 mutation has a broad spectrum of clinical phenotypes including systemic infections, lymphedema, cytopenias, MDS and AML. A comprehensive profiling of transcriptome of hematopoiesis in GATA2 deficiency is currently lacking. Methods: We performed single-cell RNA sequencing of sorted bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) from eight GATA2 deficiency patients, who had various well characterized GATA2 mutations and clinically manifest myelodysplasia. We characterized transcriptomes in lineages, computationally defined cells with chromosomal abnormalities, and described gene expression of these cells. Results: Mapping patients’ cells onto normal hematopoiesis, we observed preferred deficiency in lymphoid and myeloid progenitors, which also was evidenced in loss of heterogeneity in gene correlations. HSPCs in patients exhibited distinct gene expression pattern and gene coexpression pattern compared with its counterparts in healthy donors. Distinct lineages show different transcriptional profiles resulting from GATA2 mutations. HSCs in patients exhibited dysregulated genes in apoptosis, cell cycle and quiescence, and had increased expression of erythroid/megakaryocytic priming programs and decreased lymphoid priming programs. Thus, the prominent deficiency in myeloid/lymphoid lineages in GATA2 deficiency was partly due to expression of aberrant gene programs in HSCs prior to lineage commitment. We computationally defined cells with chromosomal abnormalities and described gene expression of these cells. DNA repair genes were downregulated in trisomy 8 cells, possibly rendering these cells vulnerable to second-hit somatic mutations and additional chromosomal abnormalities. Cells with complex cytogenetics had defects in multi-lineage differentiation and cell cycle. Conclusion: Germline GATA2 mutations modulate gene expression and change gene coexpression patterns. Distinct lineages show different transcriptional profiles resulting from GATA2 mutations. The prominent deficiency in myeloid/lymphoid lineages in GATA2 deficiency was partly due to expression of aberrant gene programs in HSCs prior to lineage commitment.
2020-06-06 | GSE135194 | GEO
Project description:GATA2 mutant transduction of murine hematopoietic stem cells
2018-09-01 | GSE111328 | GEO