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T cells from paroxysmal nocturnal hemoglobinuria patients show an altered TNFR signaling pathway

ABSTRACT: In order to identify aberrant molecular mechanisms involved in immune targeting of HSCs in bone marrow, RNA-seq was applied to examine the transcriptome of T cell subsets from PNH patients and healthy controls. RNA seq , 3 PNH patient's T cell subsets (CD4Naive, CD4Memory,CD8Naive, CD8Memory), 3 Healthy T cell subsets (CD4Naive,CD4Memory, CD8Naive, CD8memory)

ORGANISM(S): Homo sapiens

SUBMITTER: Wangmin Qiao

PROVIDER: E-GEOD-83808 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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T cells from paroxysmal nocturnal hemoglobinuria patients show an altered TNFR signaling pathway

Project description:In order to identify aberrant molecular mechanisms involved in immune targeting of HSCs in bone marrow, RNA-seq was applied to examine the transcriptome of T cell subsets from PNH patients and healthy controls.

2016-06-29 | GSE83808 | GEO

Heterogeneous responses of hematopoietic stem cells to inflammatory stimuli are altered with age - single cell

Project description:This includes single cell RNA-seq samples for sorted LT-HSCs, ST-HSCs, and MPPs stimulated (or not) with LPS+PAM. Samples taken at 2 hours post stimulation (if applicable).

2017-07-19 | GSE100426 | GEO

Transcription profiling of lymphoblastoid cell lines isolated from healthy and Aicardi Syndrome patients

Project description:Comparison of gene expression in lymphoblastoid cell lines isolated between Aicardi Syndrome patients and a pool of healthy patients (including the patient's mothers).

2007-01-01 | E-MEXP-725 | biostudies-arrayexpress

Heterogeneous responses of hematopoietic stem cells to inflammatory stimuli are altered with age - bulk

Project description:This includes bulk RNA-seq samples for sorted LT-HSCs, ST-HSCs, and MPPs stimulated (or not) with LPS+PAM. Samples taken at various time points.

2017-07-19 | GSE100425 | GEO

Human bone marrow-derived myeloid dendritic cells show an immature transcriptional and functional profile compared to their peripheral blood counterparts and separate from Slan+ non-classical monocytes

Project description:The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.

2018-12-21 | GSE112770 | GEO

Joubert Syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro

Project description:Joubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability and a peculiar cerebellar and brainstem malformation, the ’molar tooth sign’. Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper we developed an in vitro neuronal differentiation model using patient-derived induced pluripotent stem cells (iPSCs), to evaluate possible neurodevelopmental defects in JS. To this end, iPSCs from four JS patients harboring mutations in distinct JS genes (AHI1, CPLANE1, TMEM67 and CC2D2A) were differentiated alongside healthy control cells to obtain mid-hindbrain precursors and cerebellar granule cells. Differentiation was monitored over 31 days through the detection of lineage-specific marker expression by qRT-PCR, immunofluorescence, and transcriptomics analysis. All JS patient-derived iPSCs, regardless of the mutant gene, showed a similar impairment to differentiate into mid-hindbrain and cerebellar granule cells when compared to healthy controls. In addition, analysis of primary cilium count and morphology showed notable ciliary defects in all differentiating JS patient-derived iPSCs compared to controls. These results confirm that patient-derived iPSCs are an accessible and relevant in vitro model to analyze cellular phenotypes connected to the presence of JS gene mutations in a neuronal context.

2024-02-08 | GSE254556 | GEO

Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers [ATAC HD]

Project description:ATAC-seq was used to study the chromatin landscape of T cell subsets from PBMCs healthy donors.

2022-03-08 | GSE179593 | GEO

Altered microRNA expression in individuals at high risk of type 1 diabetes

Project description:Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic insulin-producing β cells. CD4+ T cells are integral to the pathogenesis of T1D, but biomarkers that define their pathogenic status in T1D are lacking. miRNAs have essential functions in a wide range of tissues/organs, including the immune system. We reasoned that CD4+ T cells from individuals at high risk for T1D (pre-T1D) might be distinguished by an miRNA signature. We sorted CD4+ T cells from 9 healthy and 7 pre-T1D individuals into 6 subsets, namely naïve, resting regulatory (rTreg), activated regulatory (aTreg), transitional memory (Ttm), central memory (Tcm) and effector memory (Tem) cells, and then compared miRNA profiles between these subsets and between pre-T1D and healthy individuals by deep sequencing. Differential expression of miRNAs was detected in each of the CD4+ T cell subsets. For example, expression of miRNAs that induce apoptosis (miR-15a) or FOXP3 instability (miR-31) was increased in rTreg and aTreg cells, respectively, in pre-T1D individuals, whereas miR-150 was increased in Tem cells of pre-T1D individuals. Importantly, increased miR-150 expression could be detected by qRT-PCR in total CD4+ T and PBMCs of pre-T1D individuals. Consistent with it being a marker of pathogenic CD4+ T cells, we showed that miR-150 regulates IFN-γ production in mouse CD4+ T cells. Thus, comprehensive profiling identifies miRNA profiles that not only distinguish CD4+ T cell subsets but also discriminate individuals with preclinical T1D. The ability to detect differentially expressed miRNAs in total CD4+ T cells or PBMCs should facilitate clinical application of miRNAs as biomarkers.

2015-12-31 | GSE44639 | GEO

Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers [RNA HD]

Project description:RNA-seq was used to study the transcriptional landscape of T cell subsets from PBMCs of healthy donors.

2022-03-08 | GSE179609 | GEO

Characterization of transcriptomic changes induced by a gene therapy cell culture protocol to single human bone marrow and mobilized peripheral blood hematopoietic stem and progenitor cells [BM_MPB]

Project description:Here we present the single cell transcriptomes of human adult mobilized peripheral blood (mPB) and bone marrow (BM) hematopoietic stem and progenitor cell (HSPC) subsets,: long-term haematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs) and CD34+ cells before (0 h) and after 62 hours (62 h) of culture in a conditions mimicking gene therapy protocols. The culture protocol includes two hits of lentiviral transduction (lentiviral vector contains a GFP construct) and media as previously published . The objectives of this study are to investigate the effects of lentiviral transduction and cell culture in gene therapy protocol conditions on human mPB and BM haematopoietic stem and progenitor cell (HSPC) subsets. In the present study we report that 62 h of culture in gene therapy media significantly alters the transcriptome of BM and mPB subsets. In contrast, lentiviral transduction alone has a minimal effect on the transcriptome of all tested subsets. T=transduced GFP+; NT=non transduced; GFP-= transduced GFP-

2022-11-19 | GSE213370 | GEO

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