Project description:We performed scRNA-seq of non-hematopoietic cells from non-treated control (WT), BMT and aGVHD mice. Unsupervised clustering, sub-clustering based on gene expression and trajectory analysis converged on the conclusion that aGVHD likely disrupts MSC differentiation potential, especially osteogenesis.
Project description:BM cells were isolated from C57BL/6 (CD45.2) Tet2–/– mice and Tet2+/+ littermates, as well as from congenic C57BL/6.SJL (CD45.1) mice (all genotypes purchased from JAX). lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2–/– CD45.2 BM cells and 90% WT CD45.1 BM cells (2x105 Tet2–/– CD45.2 BM cells and 18x105 WT CD45.1 BM cells; total of 2x106 BM cells/recipient mouse). This group was designated ‘10% Tet2–/– BMT’ (experimental). For the control group that was designated ‘10% Tet2+/+ BMT’, lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2+/+ CD45.2 BM cells and 90% WT CD45.1 cells (2x105 Tet2+/+ CD45.2 BM cells & 18x105 WT CD45.1 BM cells, thus exclusively TET2-sufficient cells; total of 2x106 BM cells/recipient mouse). At 12 weeks post-BMT (when there is complete reconstitution of hematopoiesis from transplanted long-term HSCs), ‘10% Tet2–/– BMT’ and ‘10% Tet2+/+ BMT’ mice either received no further treatment (and examined for natural periodontal bone loss) or were subjected to LIP for 5 days.
Project description:Microglia replacement by bone marrow transplantation (Mr BMT) is an emerging strategy for replacing resident macrophages and microglia with donor-derived cells. To characterize chromatin accessibility changes associated with long-term macrophage replacement, ATAC-seq was performed on liver CD45+ immune cells isolated from 11.5-month-old naïve and Mr BMT mice. This dataset provides genome-wide profiles of accessible chromatin regions in peripheral immune cells following Mr BMT.
Project description:Donor OTUD1 deficiency significanltly ameliorates the severity of aGVHD mice. We used single cell RNA sequencing (scRNA-seq) to analyze the immune cells in aGVHD mice transferred wild type or OTUD1-deficient cells.
Project description:The goal of this study are to identify critical biomarkers distinguishing alloHSCT recipients with aGvHD from alloHSCT recipients without aGvHD in two separate cohorts. Total RNA was isolated from the peripheral blood mononucleated cells and then quantified on a Bioanalyzer. Whole transcriptome sequencing libraries (3 pairs of aGvHD and controls, 6 libraries in total) were prepared following the manufacturer’s instructions for the Whole Transcriptome Sample Prep Kit (Illumina) by GENEWIZ Company. 1148 presented significant alterations in cases with aGvHD (t test, FDR corrected P < 0.05, |fold change|>1.5). Transcriptomic pathway analysis showed that the GPL metabolism pathway was one of the most significant pathways with Bonferroni correction P value (Q value) less than 0.001, indicating that it was a critical pathway related to the development of aGvHD.
Project description:Microglia replacement by bone marrow transplantation (Mr BMT) enables efficient engraftment of donor-derived macrophages in multiple organs beyond the central nervous system. To investigate the long-term transcriptional consequences of macrophage replacement in peripheral tissues, liver macrophages were isolated from 11.5-month-old naïve and Mr BMT mice and subjected to bulk RNA sequencing. This dataset provides a comprehensive characterization of the transcriptional states of resident and donor-derived liver macrophages and enables the assessment of macrophage adaptation and tissue-specific remodeling following Mr BMT.