B7545bce-9b2c-4fb8-8278-7f4899f1638f - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006799 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:To define the mechanistic basis of clonal hematopoiesis in SDS, we investigated somatic
mutations acquired by patients with SDS followed longitudinally. This dataset includes single cell sequencing data from SDS bone marrow as well as serial samples from a single patient that went on to develop AML.
| EGAS00001004881 | EGA
Project description:This dataset includes paired WES from bone marrow samples of patients with SDS and paired bone marrow-derived fibroblasts as a germline reference. Some patients have multiple samples collected serially over time. There are 74 BAM files included in this dataset.
| EGAD00001006815 | EGA
Project description:Shwachman-Diamond syndrome (SDS) is a bone marrow failure (BMF) syndrome associated with an increased risk of myelodysplasia and leukemia. The molecular mechanisms of SDS are not fully understood. We report that primitive hematopoietic cells from SDS patients present with a reduced activity of the small Rho GTPase Cdc42 and concomitantly a reduced frequency of HSCs polar for polarity proteins. The level of apolarity of SDS HSCs correlated with the magnitude of HSC depletion in SDS patients. Importantly, exogenously provided Wnt5a or GDF11 that elevates the activity of Cdc42 restored polarity in SDS HSCs and increased the number of HSCs in SDS patient samples in surrogate ex vivo assays. Single cell level RNA-Seq analyses of SDS HSCs and daughter cells demonstrated that SDS-HSC treated with GDF11 are transcriptionally more similar to control than to SDS-HSCs. Treatment with GDF11 reverted pathways in SDS HSCs associated with rRNA processing and ribosome function, but also viral infection and immune function, p53-dependent DNA damage, spindle checkpoints, and metabolism, further implying a role of these pathways in HSC failure in SDS. Our data suggest that HSC failure in SDS is driven at least in part by low Cdc42 activity in SDS HSCs. Our data thus identify novel rationale approaches to attenuate HSCs failure in SDS.
2020-09-18 | GSE158140 | GEO
Project description:Monosomy 7 or deletion of 7q (del(7q)) frequently arise in inherited and acquired bone marrow failure, and are associated with progression to high grade Myelodysplastic Syndrome (MDS) and acute leukemia. Current non-transplant approaches to treat marrow failure may be complicated by potential stimulation of clonal outgrowth. To study the biological consequences of del(7q) within the context of a failing marrow, we utilized induced pluripotent stem cells (iPSCs) derived from patients with Shwachman Diamond Syndrome (SDS) and genomically engineered a deletion of (7q). Deletion of 7q failed to confer a relative fitness advantage in either pluripotent SDS iPSC or in iPSC-derived SDS CD34+ cells. The TGF-beta pathway was the top differentially regulated pathway in transcriptome analysis with the TGF pathway found activated in SDS-iPSCs, compared to SDS-del(7q) iPSCs. Increased phosphorylation of SMAD2 in SDS-iPSCs was reduced following del(7q) and increased upon restoration of 7q diploidy, in support of an effect of 7q dosage on the activation status of the TGF-beta pathway in SDS. Inhibition of the TGF-beta pathway rescued hematopoiesis in SDS-iPSCs and in primary bone marrow cells from SDS patients without improving hematopoiesis of the SDS-del(7q) cells. Together, these results utilizing an iPSC model of MDS in BMF identified a targetable vulnerability for potential therapeutic strategies to ameliorate bone marrow failure without promoting outgrowth of the del7q clone.
2019-07-26 | GSE118377 | GEO
Project description:Monosomy 7 or deletion of 7q (del(7q)) frequently arise in inherited and acquired bone marrow failure, and are associated with progression to high grade Myelodysplastic Syndrome (MDS) and acute leukemia. Current non-transplant approaches to treat marrow failure may be complicated by potential stimulation of clonal outgrowth. To study the biological consequences of del(7q) within the context of a failing marrow, we utilized induced pluripotent stem cells (iPSCs) derived from patients with Shwachman Diamond Syndrome (SDS) and genomically engineered a deletion of (7q). Deletion of 7q failed to confer a relative fitness advantage in either pluripotent SDS iPSC or in iPSC-derived SDS CD34+ cells. The TGF-beta pathway was the top differentially regulated pathway in transcriptome analysis with the TGF pathway found activated in SDS-iPSCs, compared to SDS-del(7q) iPSCs. Increased phosphorylation of SMAD2 in SDS-iPSCs was reduced following del(7q) and increased upon restoration of 7q diploidy, in support of an effect of 7q dosage on the activation status of the TGF-beta pathway in SDS. Inhibition of the TGF-beta pathway rescued hematopoiesis in SDS-iPSCs and in primary bone marrow cells from SDS patients without improving hematopoiesis of the SDS-del(7q) cells. Together, these results utilizing an iPSC model of MDS in BMF identified a targetable vulnerability for potential therapeutic strategies to ameliorate bone marrow failure without promoting outgrowth of the del7q clone.
2019-07-26 | GSE118372 | GEO
Project description:To define the mechanistic basis of clonal hematopoiesis in Shwachman-Diamond syndrome (SDS), we investigated somatic mutations acquired by patients with SDS followed longitudinally. This dataset includes the initial discovery cohort whole exome sequencing from bone marrow samples used to identify novel somatic mutations in patients with SDS. Paired fibroblasts serve as a germline control.
| EGAS00001004880 | EGA
Project description:Bulk RNA sequencing from patient bone marrow samples
| PRJNA643584 | ENA
Project description:IVLBCL is a rare distinct disease entity of extranodal large B-cell lymphoma . The disease is characterized by selective growth of tumor cells in the lumina of small vessels and by the absence of remarkable lymphadenopathy. We have developed patient derived xenograft IVLBCL mouse models from primary patient bone marrow samples. This dataset includes the array CGH analysis of IVLBCL tumor cells from the mouse xenograft models.
2016-08-13 | GSE72027 | GEO
Project description:This project investigates the proteomic changes in bone marrow-derived macrophages (BMDMs) from mouse under two conditions: control (Ctrl) and specialized pro-resolving mediator (SPM) treatment. The study includes 3 biological replicates per condition, aiming to identify proteins involved in macrophage function and inflammation resolution.
2025-09-01 | PXD058466 | Pride
Project description:This dataset includes amplicon based sequencing of myeloid malignancy associated genes as well as EIF6 in 99 patients with Shwachman-Diamond syndrome and 11 patients who are "SDS-like". SDS-like patients are those that have clinical features of the disease but do not have a confirmed disease-causing mutation. There are 421 samples from serial timepoints, denoted alphabetically or numerically. For each timepoint, there is a single BAM file.
| EGAD00001006800 | EGA