RNA-seq mouse donor T-cells 7 days post HSCT
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE134975 | GEO | 2019/07/27
REPOSITORIES: GEO
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Project description:RNA-seq mouse donor T-cells 7 days post HSCT
| PRJNA556902 | ENA
Project description:Reconstitution of cell lines and occurrence of complications following hematopoietic stem cell transplantation (HSCT) are regulated by genome expression. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare whole genome expression in children before and after HSCT. A total of 44 children treated with HSCT were enrolled in the study. Gene expression was measured before HSCT (pre-HSCT group; n=44) and after a median of 6 months after allogenic HSCT (post-HSCT group; n=27; all children were included in the pre-HSCT group). Neoplasms were the indication for HSCT in 73% of the patients. Whole genome expression was assessed in leukocytes using GeneChip® HumanGene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed 18 significantly different genes with defined function. These genes are responsible for proliferation and differentiation of cells (14 genes), apoptosis (8 genes), migration of cells (3 genes) and fluid/electrolyte homeostasis (2 genes). Our findings allow us to conclude that activation of genes involved in reconstitution of donor cell lines, and those related to immune reactions observed after HSCT, form the genetic background for physiological and pathological processes following HSCT.
2016-10-19 | GSE88852 | GEO
Project description:To track for T cell clones from donor memory T cell fraction infused after abT/CD19-depleted allogenic HSCT we performed TCR beta repertoire sequencing. Patient peripheral blood repertoire was sequenced in two timepoints (p3 and p4: d120-180 and d360-500). Reperotoires for bulk and CD4+ or CD8+ cells from CD45RA-depleted donor apheresis were obtained for most donor-recipient pairs. TCR beta cDNA libraries were prepared using previously published protocol (Zvyagin I.V. et al., Leukemia, 2017). Libraries were sequenced on Illumina NextSeq 500/550 and HiSeq2000/2500 in pair-end mode with read length 100-150 bp. MiGEC software were used for demultiplexing and unique molecular identifier sequence extraction software (https://github.com/mikessh/migec).
2020-07-01 | E-MTAB-8874 | biostudies-arrayexpress
Project description:This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).
| 2129398 | ecrin-mdr-crc
Project description:In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), severe graft-versus-host disease (GVHD) is tied to failed donor plasmacytoid DC (pDC) reconstitution. The mechanism whereby GVHD causes donor pDC defects and the precise role donor pDCs play in GVHD remain poorly understood. pDCs develop from HSCs in successive stages through Flt3 signaling-dependent differentiation, beginning as multi-potent progenitors (MPPs) and later becoming common DC progenitors. We observed that MPPs were critical for sustaining pDCs and were severely depleted during GVHD. Loss of MPPs was associated with decreased amounts of MPP-producing HSCs and mTOR activation-induced cell death of proliferating MPPs. Additionally, GM-CSF derived from alloreactive T cells subverted MPP production of pDCs. Together, GVHD and alloreactive T cells caused donor pDC defects by impairing the generation, maintenance and differentiation of HSCs and MPPs. Importantly, pDCs suppressed the proliferation and expansion of activated autologous CD4+ T cells via a type I-IFN signaling-dependent mechanism. Transfer of donor pDCs early after transplantation repressed GVHD and preserved potent GVL effects, significantly improving the survival of leukemia mice undergoing allo-HSCT. Our findings identify novel strategies that improve the recovery of donor pDCs early after allo-HSCT and thus may represent an effective therapy to control GVHD. Our findings have broad implications for other diseases in which functional DC development is impaired, such as chronic infections, autoimmunity and cancer.
2021-01-06 | GSE143788 | GEO
Project description:Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however the mechanisms are incompletely understood. We followed a group of patients (n=18) receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy we compared the immunological changes induced by HSCT in responders and non-responders.
2019-01-23 | GSE100922 | GEO
Project description:The prediction of acute graft-versus-host disease (aGvHD) post allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critical for treatment decisions. The granulocytic myeloid-derived suppressor cells (G-MDSCs) show a fast recovery post-transplantation and constituted the major part of peripheral blood in the early phase after allo-HSCT. These cells were previously believed to exhibit immunosuppressive properties. However, they also promote inflammation under specific conditions. Thus, we conducted a comprehensive study of G-MDSCs from 82 patients after allo-HSCT within 90 days to elucidate the role of them in post-transplantation immunity. Strikingly, our results showed that G-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing aGvHD. Besides, adoptive transfer of G-MDSCs from patients into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs showed immunosuppressive features, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that a total of 1445 genes were differentially expressed. Genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. After the genetic overlap analysis, DERL1 may be the hub-gene. Our findings elucidate the alteration in the immune characteristics of G-MDSCs within the first 90 days post allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 could serve as a predictive indicator for aGvHD.
2024-06-25 | GSE260477 | GEO
Project description:Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity, but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.
2020-12-21 | GSE161160 | GEO