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Spatial transcriptomic in synovial tissue of psoriasis (Ps) and psoriatic arthritis (PsA) humanized mice.

ABSTRACT: Spatial transcriptomics was performed in areas enriched with CD45+ immune cells or CD8+ T cells. Data was generated with 12 mice: 4 NSG-SGM3 mice reconstituted with blood fo 4 healthy individuals, 4 NSG-SGM3 mice reconstituted with blood from 4 PsA patients and 4 NSG-SGM3 mice reconstituted with blod cells of 4 Ps patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE268695 | GEO | 2024/05/30

REPOSITORIES: GEO

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Immune Restoring (IR) CAR-T Cells Display Superior Antitumor Activity and Reverse Immunosuppressive TME in a Humanized ccRCC Orthotopic Mouse Model

Project description:Here we report a humanized clear cell renal cell carcinoma (ccRCC) orthotopic NSG-SGM3 mouse model (hccRCC-NSG-SGM3) with reconstituted human lymphocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) bearing human ccRCC skrc-59 cells under the kidney capsule. Human leukocyte antigen (HLA) matched CD34+ HSCs were used for the humanization to reduce T cell alloreactivity against skrc-59 human ccRCC cells. Tumors were collected and sorted for CD45+ tumor infiltrated leukocytes (TILs) to profile the tumor microenvironment (TME) in hccRCC-NSG-SGM3. By comparing to patient data from prospective clinical trials of the anti-PD-1 monoclonal antibody (mAb) nivolumab in advanced ccRCC, the results demonstrated that the CD45+ TILs from hccRCC-NSG-SGM3 reconstitutes most CD45+ cell types, including NK cells, dendritic cells, exhausted CD8 T cells, regulatory T cells (Tregs), that are observed in advanced ccRCC patient TME. Furthermore, Anti-carbonic anhydrase IX (CAIX) G36 immune restoring (IR) chimeric antigen receptor (CAR) T cells secreting PD-L1 targeted immune checkpoint inhibitor (ICI) mAb (G36-PDL1) exhibited superior tumor control compared to G36 CAR-T cells with anti-SARS mAb (G36-SARS) and anti-BCMA A716 CAR-T cells with anti-PD-L1 mAb (A716-PDL1). In addition, G36-PDL1 CAR-T cells restored active anti-tumor immunity at tumor site uncovered by 10X genomics single cell RNA sequencing (scRNA-seq) and single cell T cell receptor sequencing (scTCR-seq).

2024-01-25 | GSE210664 | GEO

Single-cell RNA sequencing reveals human leukocyte responses in humanized mice with contusive spinal cord injury

Project description:Next-generation humanized mouse models and single-cell RNA sequencing approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). Our behavioural studies firstly show that the benefits of immunocompromise on SCI recovery are lost with the introduction of human immune cells into these mice. Using flow cytometry and scRNAseq, we then describe the composition of their circulating immune cell repertoire, and how the human immune cell population transcriptionally changes following injury. Through comparisons of SCI with naïve and sham-operated mice, we also provide insight into the transcriptional signature of human leukocytes in association with SCI-induced systemic immune depression syndrome (SCI-IDS). We further highlight the local activating influence of the spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human cells. We lastly applied an integrated bioinformatics approach to determine where immune responses in humanized NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.

2023-11-01 | GSE236293 | GEO

Microarray analysis of the migrating human CD4+ T cell population from the spleen of humanized mice in response to treatment with Teplizumab or hIg

Project description:In order to identify genes expressed by cells that leave the spleen, the spleens were harvested from untreated reconstituted humanized mice (N=4) and a single cell suspension was prepared . The cultures were treated with either teplizumab (anti human CD3 hOKT3g1(Ala-Ala)) or hIg for 18 hrs in vitro. Splenocytes were also harvested 18 hrs after reconstituted mice (N=4) were treated with teplizumab in vivo. The humanized mice used where NOD/SCID IL2gc-/- (NSG) reconstituted with human CD34+ at birth. Total RNA was obtained form sorted human CD4 splenocytes 18 hours post treatment. Comparsons were made between the treatment groups.

2012-02-27 | E-GEOD-34163 | biostudies-arrayexpress

Microarray analysis of the migrating human CD4+ T cell population from the spleen of humanized mice in response to treatment with Teplizumab or hIg

2012-02-27 | GSE34163 | GEO

Treg transcriptomic profile in NSG, NSG+Thymus humanized mice and healthy donors (HD)

Project description:RNA sequencing was performed on RNA extracted from human Treg cells from NSG, NSG+Thymus humanized mice and healthy donors

2021-11-02 | GSE186881 | GEO

Whole Genome Sequencing on OCIAML-22

Project description:Donor_OCIAML22_bulk: The donor (unsorted) that was used to generate OCI-AML22. OCI-AML22_bulk_1month_inVitro: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then sequenced. OCI-AML22_graft_CD34minus_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34- fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34-) OCI-AML22_graft_CD34positive_WGS: The donor (unsorted) that was used to generate OCI-AML22 was expanded for 1 month in vitro, then injected in NSG-SGM3 mice. 21 weeks after injection, cells from 5 mice injected with 5 mice injected with 1475 cells per mice and 4 mice injected with 469 cells per mice were sorted. The human CD34+ fraction was sequenced (CD45h+CD45m-7aad-annexinV-CD34+)

| EGAS00001006513 | EGA

Humanized mice for investigating SARS-CoV-2 lung infection and associated human immune responses

Project description:There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L) could be infected efficiently by SARS-CoV-2, and that live viruses capable of infecting human Vero cells were found in the HL grafts and multiple organs from infected NSG-L mice. RNA-seq examination identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation, and pulmonary fibrosis between HL grafts from infected and control NSG-L mice. Furthermore, when infecting humanized mice with human immune system (HIS) and autologous HL grafts (HISL mice), the mice had bodyweight loss and hemorrhage in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live viruses at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.

2022-12-31 | GSE175900 | GEO

Human Whole Blood: Psoriatic Arthritis [PsA] vs. Cutaneous Psoriasis Without Arthritis [PsC] vs. Controls

Project description:Transcriptional profiling of human whole blood comparing PsA, PsC, and unaffected controls

2014-09-24 | GSE61281 | GEO

Treg transcriptomic profile in NSG, NSG+Thymus humanized mice and healthy donors (HD)

Project description:Treg transcriptomic profile in NSG, NSG+Thymus humanized mice and healthy donors (HD)

| PRJNA776635 | ENA

Single-cell RNA sequencing experiment of aortic arch and root samples from mice with rHDL and PS@rHDL treatment

Project description:The experiment was performed by using Apoe-/- mice fed on a high-fat, high-cholesterol diet (Western diet, WD) for either 6 weeks. The samples were collected from aortic arch and root of two different groups of mice: one treated with rHDL (reconstituted HDL nanoparticles), and the other with PS@rHDL (reconstituted HDL nanoparticles incorporating phosphatidylserine).

2024-08-08 | E-MTAB-14252 | biostudies-arrayexpress

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