Bulk RNA-seq of peripheral organs from naïve, tBMT, and Mr BMT mice under homeostatic and inflammatory conditions
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE334348 | GEO | 2026/08/19
REPOSITORIES: GEO
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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.
2026-08-19 | GSE334349 | GEO
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.
2026-08-19 | GSE334350 | GEO
Project description:Recent advances in cell-based therapies have demonstrated therapeutic safety and efficacy for a variety of diseases. However, significant challenges remain in their development for the treatment of neurological disorders. Preclinical studies have explored microglial replacement strategies utilizing bone marrow transplantation and CSF1R-inhibitor (CSF1Ri) treatment. However, these approaches often require highly invasive strategies and result in engrafted cells that remain transcriptionally and functionally distinct from microglia. To assess less invasive microglia replacement strategies capable of preserving microglial ontogeny, we developed a Csf1r-G793A knockin mouse. We found G793A mice develop typical microglial densities and peripheral hematopoietic populations which exhibit broad CSF1Ri resistance enabling widespread microglia replacement following direct intraparenchymal injection or bone marrow transplantation. Furthermore, we demonstrate that widespread microglia replacement can be achieved via less invasive intracisternal delivery of CSF1Ri-resistant murine and iPSC-derived human microglia. Together with the accompanying study by Lombroso and colleagues, our findings demonstrate that G793A mice provide a robust and broadly applicable source of engraftable donor microglia and peripheral macrophages for the preclinical investigation of microglia replacement strategies.
2025-11-25 | GSE311140 | GEO
Project description:Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia associated disorders. However, most of attempts are failed due to low replacement efficiencies, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB) and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.
2020-07-31 | GSE155499 | GEO
Project description:Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia associated disorders. However, most of attempts are failed due to low replacement efficiencies, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB) and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.
2023-07-31 | GSE136364 | GEO
Project description:To investigate the pathological effect of miR-126 on the progression of acute myeloid leukemia (AML) induced by AML1-ETO9a (AE9a), we conducted a series of mouse bone marrow transplantation (BMT) assays with the following groups: AE9a (primary donor cells were wild-type mouse bone marrow progenitor (i.e., lineage negative; Lin-) cells retrovirally transduced with MSCV-PIG-AE9a), AE9a+miR-126 (primary donor cells were wild-type mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG-AE9a-miR-126), and miR-126KO+AE9a (primary donor cells were miR-126 knockout mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG-AE9a), along with a control group (primary donor cells were wild-type mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG empty vector). The control group was only used in the primary and secondary BMT assays, whereas the three leukemic groups including AE9a, AE9a+miR-126 and miR-126KO+AE9a were used in four passages (i.e., primary, secondary, tertiary and quaternary) of BMT assays. Then, gene expression profiling was conducted with bone marrow samples collected from different groups to decipher the molecular mechanisms underlying miR-126 effects on leukemia initiation and progression and maintenance and self-renewal of leukemia stem/initiating cells. A total of 39 mouse bone marrow samples including 36 mouse AML samples with AE9a, AE9a+miR-126, and miR-126KO+AE9a collected from the 1st, 2nd, 3rd and 4th passages of BMT recipient mice (3 mice for each group in each passage), along with 3 normal controls from the 1st passage of BMT, were analyzed by use of Affymetrix GeneChip Mouse Gene 2.0 ST Array (Affymetirx, Santa Clara, CA). For each sample, the CD45.1+ cells (i.e., transplanted donor cells) were sorted with flow cytometry from whole BM cells collected from BMT recipient mice at the end stage. Then total RNA was isolated by use of miRNeasy extraction kit (Qiagen, Valencia, CA).
2015-09-07 | E-GEOD-65939 | biostudies-arrayexpress
Project description:To investigate the pathological effect of miR-126 on the progression of acute myeloid leukemia (AML) induced by AML1-ETO9a (AE9a), we conducted a series of mouse bone marrow transplantation (BMT) assays with the following groups: AE9a (primary donor cells were wild-type mouse bone marrow progenitor (i.e., lineage negative; Lin-) cells retrovirally transduced with MSCV-PIG-AE9a), AE9a+miR-126 (primary donor cells were wild-type mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG-AE9a-miR-126), and miR-126KO+AE9a (primary donor cells were miR-126 knockout mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG-AE9a), along with a control group (primary donor cells were wild-type mouse bone marrow progenitor (i.e., Lin-) cells retrovirally transduced with MSCV-PIG empty vector). The control group was only used in the primary and secondary BMT assays, whereas the three leukemic groups including AE9a, AE9a+miR-126 and miR-126KO+AE9a were used in four passages (i.e., primary, secondary, tertiary and quaternary) of BMT assays. Then, gene expression profiling was conducted with bone marrow samples collected from different groups to decipher the molecular mechanisms underlying miR-126 effects on leukemia initiation and progression and maintenance and self-renewal of leukemia stem/initiating cells.
2015-09-07 | GSE65939 | GEO
Project description:Bone Marrow Transplantation (BMT) depends greatly on transendothelial migration of stem cells from bloodstream to bone marrow. Therefore Bone Marrow Endothelial Cells (BMECs) becomes an essential component for successful BMT. Since BMT requires prior radiation therapy therefore it is necessary to study the behaviour of BMEC in irradiated and radiprotective conditions. We have conducted transcriptome profiling of Bone Marrow Endothelial Cells (BMECs) to identify the signalling mechanisms required for transendothelial migration to bone marrow under irradiated and radioprotected conditions.
2020-09-30 | GSE108722 | GEO
Project description:Genetic evidence indicates that microglial dysfunctions contribute to the development and progression of various neurologic diseases, emphasizing microglia replacement as a promising therapeutic strategy. However, traditional bone marrow transplantation (BMT) aimed at replenishing brain microglia faces challenges due to low efficiency and potential brain injury from preconditioning with irradiation or chemotherapy. Moreover, the BM-derived cells that migrate to the brain fail to replicate the characteristics of resident microglia. Here, we present a simple yet highly effective microglia transplantation strategy devoid of any conditioning, termed "Tri-Cyclic Microglial Depletion for Transplantation" (TCMDT). This approach leverages three cycles of microglial depletion using the CSF1R inhibitor PLX3397, creating a critical window for the efficient engraftment of exogenous microglia. Notably, transplanting primary cultured microglia via the TCMDT strategy achieves their full restoration to the identity and functions of native microglia. To evaluate the therapeutic potential, we applied our strategy to a Sandhoff disease mouse model, a form of neurodegenerative lysosomal storage disorder (LSD) caused by Hexb deficiency. The results revealed that our strategy facilitated the efficient replacement of deficient microglia, leading to a notable decrease in neurodegeneration and an enhancement in motor performance. Similarly, in an Alzheimer's disease (AD) mouse model carrying the Trem2 R47H mutation, our transplantation strategy corrected microglial dysfunction and alleviated AD-related pathology. Overall, our study presents a practical approach for microglia replacement that is simple, efficient, and safe, offering significant therapeutic potential for treating microglia-associated disorders.
2025-03-06 | GSE272257 | GEO
Project description:JAK2V617F is one of the most common mutations in clonal hematopoiesis of indeterminate potential (CHIP) and a major driver of myeloproliferative neoplasms (MPN). To determine the impact of the low frequency JAK2V617F clone on both the hematopoietic system and the bone marrow (BM) stroma, we developed a traceable murine JAK2V617F MPN model where the disease is induced in unconditioned bone marrow transplantation (BMT) recipients. Whole BMT was performed via a single tail vein injection of 5.0x106 cells into unconditioned C57BL/6 Ptprca CD45.1+ recipient mice using CD45.2+ donor cells carrying JAK2V617F isolated from a Poly I:C inducible MPN-like model. BMT resulted in a PV-like phenotype (elevated hematocrit and leukocytosis) with an average donor cell chimerism in peripheral blood of 2.74%. Eight months after BMT, RNA-seq analysis of whole BM sorted according to CD45.1/CD45.2 expression showed significant upregulation of early erythroblast- and myeloid cell-specific transcripts, as well as downregulation of lymphoid transcripts in donor-derived cells compared to controls. Surprisingly, recipient-derived cells also showed upregulation of myeloid- and erythroblast-related transcripts, indicating a skewing of the non-JAK2V617F carrying recipient hematopoietic system towards an MPN-like phenotype. In addition, RNA-seq analysis of the BM stroma from JAK2V617F BMT recipients 28-32 weeks post-BMT indicated significant loss of osteo-mesenchymal transcripts. Consistently, micro-CT imaging indicated loss of trabecular bone. Our model uncovers the impact of JAK2V617F donor cells on the host BM microenvironment and hematopoietic system, driving an MPN phenotype even with low donor cell chimerism within unconditioned recipients. The observation that BMT recipient’s hematopoietic cells, which do not carry JAK2V617F, acquire unique transcriptomic and phenotypic profiles suggests that the MPN clone not only impacts hematopoiesis-supporting stroma but profoundly influences unmutated cells, challenging our current understanding and therapeutic approaches to MPNs and other CHIP-associated diseases.
2025-08-20 | GSE278496 | GEO