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Comparison of pDCs isolated from recipients of STAT1+/+ vs. STAT1-/- bone marrow

ABSTRACT: The goal of this study is to determine if pDCs reconstituted from T cell depleted allogeneic STAT1-/- bone marrow express genes that contribute to Graft versus host disease (GVHD) resistance as compared to STAT1+/+ bone marrow

ORGANISM(S): Mus musculus

PROVIDER: GSE59731 | GEO | 2014/07/25

SECONDARY ACCESSION(S): PRJNA256073

REPOSITORIES: GEO

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Comparison of pDCs isolated from recipients of STAT1+/+ vs. STAT1-/- bone marrow

Project description:The goal of this study is to determine if pDCs reconstituted from T cell depleted allogeneic STAT1-/- bone marrow express genes that contribute to Graft versus host disease (GVHD) resistance as compared to STAT1+/+ bone marrow Lethally irradiated B6 x C3H.SW mice were transplanted with T cell depleted 129 or 129 STAT1-/- bone marrow. 14 days later, pDCs were isolated from spleens by magnetic cell selection, and pooled from 12 mice/group. cDNA was generated and hybridized to an Affymetrix genechip mouse genome 430 2.0 array. Samples were normalized by RMA algorithm to a log2 intensity value and analyzed by Ingenuity Pathway Analysis v8.5 software.

2014-07-25 | E-GEOD-59731 | biostudies-arrayexpress

STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration

Project description:The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment. To assess impacts of T-cell-driven injury on distinct epithelial constituents, we performed single cell RNA sequencing on intestinal crypts following experimental BMT. Intestinal stem cells (ISCs) from GVHD mice exhibited global transcriptomic changes associated with a substantial Interferon-γ response and upregulation of STAT1. To determine its role in crypt function, STAT1 was deleted within murine intestinal epithelium. Following allo-BMT, STAT1 deficiency resulted in reduced epithelial proliferation and impaired ISC recovery. Similarly, epithelial Interferon-γ receptor deletion also attenuated proliferation and ISC recovery post-transplant. Investigating the mechanistic basis underlying this epithelial response, ISC STAT1 expression in GVHD was found to correlate with upregulation of ISC c-Myc. Furthermore, activated T cells stimulated Interferon-γ- dependent epithelial regeneration in co-cultured organoids, and Interferon-γ directly induced STAT1-dependent c-Myc expression and ISC proliferation. These findings illustrate immunologic regulation of a core tissue stem cell program after damage and support a role for Interferon-γ as a direct contributor to epithelial regeneration.

2024-09-09 | GSE276126 | GEO

Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCs

Project description:Hdac3 is highly expressed in pDCs, and its deficiency led to substantially impaired development of pDCs, but not cDCs in bone marrow (BM) and spleen. Meanwhile,further investigation demonstrated that HDAC3 was required for the differentiation of pDC from progenitors at different differentiation stages in vitro. Cut & Tag analysis of H3K27ac level in HDAC3 deficient bone marrow pDCs compared with control pDCs, showed that H3K27ac level significantly increased on cDC related genes with PU.1 binding sites in HDAC3 knockout pDCs.

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Single cell RNA sequencing of mouse donor T cells after graft-versus-host disease (GVHD) model

Project description:Lethally irradiated mice were transferred with bone marrow cells together with allogeneic Treg cells isolated from CD226+/+ TIGIT+/+, CD226-/- TIGIT+/+, CD226+/+ TIGIT-/-, or CD226-/- TIGIT-/- mice, followed by allogeneic wild-type Tconv cells two days later to induce acute GVHD. We performed scRNA sequencing of donor T cells isolated from the spleen of recipient mice eight days after GVHD induction.

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Signatures of GVHD and Relapse after Post-Transplant Cyclophosphamide Revealed by Immune Profiling and Machine Learning [15065R]

Project description:Lymphocyte subsets (CD8, CD4 Tconv, CD4 Treg) were sorted from patients' peripheral blood obtained on day 28 after matched-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy) as a single agent GVHD prophylaxis (NCT00809276). Cohort of patients developed GVHD, or remained GVHD-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD.

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Project description:Lymphocyte subsets (CD8, CD4 Tconv, CD4 Treg) were sorted from patients' peripheral blood obtained 180 days after matched-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy) as a single agent GVHD prophylaxis (NCT00809276). Cohort of patients developed GVHD, or remained GVHD-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD.

2021-09-28 | GSE182678 | GEO

Expression analysis from Runx2-deficient pDCs from mouse

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2013-09-30 | E-GEOD-49859 | biostudies-arrayexpress

Mus musculus

Project description:Comparison of pDCs isolated from recipients of STAT1+/+ vs. STAT1-/- bone marrow

| PRJNA256073 | ENA

Expression analysis from Runx2-deficient pDCs from mouse

2013-09-30 | GSE49859 | GEO

Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCs

Project description:Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCs

| PRJNA809374 | ENA