Single-cell transcriptomic analysis of PB and BM NK cells from severe aplastic anemia patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE214207 | GEO | 2022/09/29
REPOSITORIES: GEO
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Project description:Single-cell transcriptomic analysis of PB and BM NK cells from severe aplastic anemia patients
| PRJNA884365 | ENA
Project description:During immune-mediated severe aplastic anemia (SAA) monocytes (CD11b+ Ly6C+ Ly6G-) signficantly increase by both frequency and number within the bone marrow. We isolated BM monocytes from F1 hybrid mice (C57BL/6;Balb/c) induced with SAA via the splenocyte-transfer model. We utilized single-cell RNA sequencing (scRNA-seq) to analyze the heterogenity of BM monocytes during SAA.
2023-07-19 | GSE237388 | GEO
Project description:plasma of SAA patients (n = 14) and healthy donors (n =15)
2021-10-09 | PXD029024 |
Project description:Pediatric severe aplastic anemia (PSAA) is a rare and life-threatening disease, which has been suggested to result from deficiency in essential cytokines or growth factors in bone marrow mesenchymal stem cells (MSCs). In this study, we examined expression profiles of the essential cytokines and growth factors, which were involved in proliferation and differentiation of MSC, in 5 PSAA patients using oligonucleotides microarrays. Following evaluation of gene expression patterns using cluster analysis and gene ontology classifications, fifteen potential genes that were cell proliferation- and cytokine-related and significantly down-regulated in PSAA were selected. The findings of the microarray analysis were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Interestingly, silencing of chemokine ligand 12 (CXCL12, also named stromal cell-derived factor 1, SDF1) or hepatocyte growth factor (HGF) gene expression reduced cell growth and response to adipogenic factor-induced differentiation, but increased osteogenesis, which possibly derived from hematopoietic stem cells (HSCs). Re-introduction of the CXCL12 gene or exogenously added HGF, on the other hand, partially recovered cell function of PSAA MSC. These results suggest that gene expression in PSAA MSC is globally down-regulated by a yet-to-be-determined mechanism. Among these down-regulated genes, CXCL12 and HGF played vital roles in regulating cell growth and differentiation. Mesenchymal stem cells from five pediatric SAA patients vs. MSC from five healthy donors, which were pooled together.
2011-11-19 | E-GEOD-33812 | biostudies-arrayexpress
Project description:Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. The achievement of transfusion independence confirmed the clinical benefit of this approach. Increase in marrow cellularity and CD34+ cells suggested a recovery to a more functioning bone marrow. Further in its development, eltrombopag was associated with standard horse ATG plus cyclosporine in first line, producing increases in overall (at about 90%) and complete response rates (at about 40%) and leading to transfusion independence and excellent survival. Interestingly, best results were observed when all drugs were started simultaneously. The cumulative incidence of clonal cytogenetic abnormalities to date has compared favorably with the vast experience with IST alone in SAA. Longer follow-up will help in define these long-term risks. In this review, the development of eltrombopag in SAA will be discussed.
| S-EPMC6234374 | biostudies-literature
Project description:Since the approval of horse antithymocyte globulin (ATG) decades ago, there was a long hiatus in therapies with activity in severe aplastic anemia (SAA). This scenario changed in 2014 when eltrombopag, a thrombopoietin receptor agonist, was approved for SAA after an insufficient response to initial immunosuppressive therapy (IST). The basis for this approval was the observation of single-agent activity of eltrombopag in this patient population, where 40% to 50% recovered blood counts at times involving >1 lineage. The achievement of transfusion independence confirmed the clinical benefit of this approach. Increase in marrow cellularity and CD34+ cells suggested a recovery to a more functioning bone marrow. Further in its development, eltrombopag was associated with standard horse ATG plus cyclosporine in first line, producing increases in overall (at about 90%) and complete response rates (at about 40%) and leading to transfusion independence and excellent survival. Interestingly, best results were observed when all drugs were started simultaneously. The cumulative incidence of clonal cytogenetic abnormalities to date has compared favorably with the vast experience with IST alone in SAA. Longer follow-up will help in define these long-term risks. In this review, the development of eltrombopag in SAA will be discussed.
| S-EPMC6245975 | biostudies-literature
Project description:BackgroundNatural killer (NK) cells play important immunoregulatory roles in the immune pathogenesis of severe aplastic anemia (SAA). Our previous research showed that SAA caused a decrease in T cell immunoglobulin mucin-3 (TIM3) expression on NK cells. Here we investigated the expression of surface receptors, and the cytotoxicity of peripheral TIM3+ NK and TIM3- NK cells in patients with SAA.MethodsThe expressions of surface receptors and cytoplasmic protein of TIM3+ NK and TIM3- NK cells from peripheral blood were detected by FCM. The functions of mDCs, and apoptosis rate of K562 cells after co-culture with TIM3+ NK and TIM3- NK cells were maesured by FCM. Westren-blot was used to detect the changes of TIM3+ NK and TIM3- NK signaling pathway proteins (AKT, P-AKT) and compare the functional activity of the two groups.ResultsActivating receptors NKG2D and Granzyme B were higher, while inhibiting receptors NKG2A, CD158a and CD158b were lower on TIM3- NK cells compared with TIM3+ NK cells in patients with SAA. In SAA, the expression of CD80 and CD86 on mDCs (Myeloid dendritic cells) was significantly decreased after incubation with TIM3- NK cells. The apoptosis rate (AR) of K562 cells was significantly increased after being incubated with TIM3- NK cells in SAA. The level of signal pathway protein AKT of TIM3- NK cells in SAA was similar to that of TIM3+ NK cells, and the levels of P-AKT and P-AKT/AKT ratio of TIM3- NK cells were significantly higher than those of TIM3+ NK cells.ConclusionsTherefore, TIM3 exerts its inhibitory effect on NK cells and participates in the immune pathogenesis of SAA. Low expression of TIM3 contributes to the enhancement of NK cell activity which in turn inhibits the immune activation state of SAA and improves the disease state. Our research may aid the development of new therapeutic strategies based on TIM3-NK cells infusion for the treatment of SAA.
| S-EPMC10956726 | biostudies-literature
Project description:We compared transcriptome of different types of NK cells including obtained from peripheral Blood (PB-NK), derived from human ES cell, H9-NK, derived from human iPSC (iPSC-NK), derived from CD34+ cells from umbilical cord blood (UCB-NK), NKcell line (NK92) and 3 cancer cell lines (K562, Raji and Jurkat). When comparing the similarity of the NK cells populations by the number of differentially expressed genes to iPSC NK cells, there were the fewest differentially expressed genes in the comparison with the UCB NK cells, followed by the PB-NK cells, followed by the H9 embryonic stem cell derived-NK cells and lastly by the NK92 cell line.
2020-10-12 | GSE150806 | GEO
Project description:Hematopoietic stem cell transplantation (bone marrow transplantation [BMT]) is the only curative treatment of severe aplastic anemia. BMT from an human leukocyte antigen (HLA)-matched sibling donor is the standard of care for young patients; immunosuppressive therapy is used for older patients or those lacking matched sibling donors. Patients with refractory or relapsed disease are increasingly treated with HLA haploidentical BMT. Historically, haploidentical BMT led to high rates of graft rejection and graft-versus-host disease. High-dose post transplant cyclophosphamide, which mitigates the risk of graft-versus-host disease, is a major advance. This article provides an overview of the haploidentical BMT approach in severe aplastic anemia.
| S-EPMC6063510 | biostudies-literature
Project description:Immune aplastic anemia (AA) is a life-threatening bone marrow (BM) failure disorder driven by an autoimmune T cell attack against the hematopoietic stem and progenitor cells (HSPCs). However, the autoantigen targets and the role of other immune cells are unknown. Here, by combining scRNA+TCRαβ-seq, TCRβ-seq, flow cytometry and plasma cytokine profiling of >250 patients with AA, >250 patients with other hematological disorders and >1,000 healthy controls, we identify NK cells and CD8+ TEMRA cells expressing NK receptors with AA-associated TCRB-seq motifs as the most dysregulated immune cell populations in AA BM. Functional co-culture experiments with scRNA-TCRαβ-seq readout utilizing primary HSPCs and immune cells (in total 55 conditions) provide evidence that NK cells alone cannot kill HSPCs, but sensitize them to CD8+ T cell mediated killing. Furthermore, HSPCs induce strong activation of T cell clones with CD8+ TEMRA NK-like phenotype and AA-associated TCR motifs. To conclude, our results reveal convergent evolution of innate and adaptive immune cells in AA, where NK cells support CD8+ T cell mediated autoimmunity.
2024-12-12 | E-MTAB-13484 | biostudies-arrayexpress