Mus musculus
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ABSTRACT:
PROVIDER: PRJNA309234 | ENA |
REPOSITORIES: ENA
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Project description:Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages. CD45.1+CD45.2+ yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages from the bronchoalveolar lavage were sorted from wild type CD45.1+CD45.2+ mice of indicated ages. From part of these samples RNA was isolated. The other part was transferred intranasally into the lungs of neonate Csf2rb-/- mice. 6 weeks post-transfer, transfer-derived CD45.1+CD45.2+ alveolar macrophages were sorted from the bronchoalveolar lavage. Wild type CD45.1+CD45.2 alveolar macrophages from the bronchoalveolar lavage of 6 week old mice were sorted as control. 36 samples (arrays) in total. RNA was isolated, amplified with Nugene pico kit, converted to cDNA and then hybridised on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.
2016-03-01 | E-GEOD-76999 | biostudies-arrayexpress
Project description:Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages.
2016-03-01 | GSE76999 | GEO
Project description:Comparative genomic analysis of basal and LPS-induced expression patterns of bone marrow derived macrophages and bone marrow resident macrophages demonstrates completely divergent transcriptome profile and indicates/confirms the existance of two distinct monocyte/macrophage populations in murine bone marrow. Most resident tissue macrophages descent from embryonic precursors of the yolk sac but inflammatory and bone marrow (BM) macrophages are considered to develop from hematopoietic stem cells (HSCs) in the BM. We now identified a novel subpopulation of resident CD163+ macrophages in the BM which were phenotypically and functionally distinct from classical BM-derived macrophages. Bioinformatics analysis of transcriptoms indicated a unique immune-modulatory phenotype of CD163+ macrophages. Cell fate studies in Csf1rMer-iCre-Mer;RosaLSL-GFP mice demonstrated that resident CD163+ macrophages of the BM do not develop from HSCs but descent from embryonic progenitors in the yolk sac strictly dependent on transcription factor IRF8. In contrast to other yolk sac derived tissue macrophages CD163+ cells seem to play a relevant role in infections and sterile inflammation. IRF8-/- mice lacking this population are highly sensible to S. aureus infections. Thus, CD163 defines a macrophage population resident in the bone marrow but originating from yolk sac progenitors which exhibits immune-modulatory properties under different inflammatory conditions. We used quantitative RNA-seq to perform whole transcriptome analysis and compare the transcriptomes of resident CD163+ BM macrophages and classical CD163- BMDM in steady state and after LPS stimulation.
2017-01-31 | GSE92618 | GEO
Project description:Although classified as hematopoietic cells, tissue-resident macrophages are selfrenewing and maintained independently of adult hematopoiesis. While most macrophages originate from embryonic precursors that seed tissues prior to birth, their exact origin is unknown. Using an in utero macrophage depletion strategy and fatemapping of yolk sac (YS) and fetal liver (FL) hematopoiesis, we found that YS macrophages are the main precursors of microglia, while most other macrophages derive from fetal monocytes. Both YS macrophages and fetal monocytes arise from erythro-myeloid progenitors (EMP) generated in the YS. In the YS, EMP gave rise to macrophages without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal monocytes that then seed embryonic tissues to differentiate into macrophages. Thus, adult tissue-resident macrophages established from HSC-independent embryonic precursors arise from two different developmental programs. 12 samples of progenitors, monocytes or macrophages are analyzed from 2 to 4 replicate. Each replicate derived from at least 5 embryos or adult mice
2015-04-23 | E-GEOD-66970 | biostudies-arrayexpress
Project description:Tissue-resident macrophages such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes as well as infiltrating, gut and dermal macrophages derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knock-outs and lineage tracing, but their applicability to human development has not been formally demonstrated. Here we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knock-out strategy we show that human iPSC-derived monocytes/macrophages develop in a MYB-independent, RUNX1 and SPI1 (PU.1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages such as alveolar and kidney macrophages, microglia, Kupffer and Langerhans cells.
2017-01-07 | GSE93285 | GEO
Project description:Microglia, the brain-resident macrophages, play key roles in neurodevelopment and aging, including neurogenesis, synaptic pruning, and myelination. Dysregulated microglia are implicated in various central nervous system (CNS) disorders. Developing safe microglia replacements and eliminating toxic microglia are promising but challenging approaches for treating CNS diseases. Microglia uniquely originate from primitive yolk-sac hematopoiesis, unlike other tissue-resident macrophages that arise from the postnatal bone marrow. Previous studies show that peripheral macrophages fail to adopt microglial characteristics after transplantation. We aim to understand the transcriptional networks underlying the ontological and environmental differences between microglia and peripheral macrophages, which may guide therapeutic strategies. Using human stem cell-derived hematopoietic progenitors (iHPCs) in a humanized mouse model deficient in resident microglia, we demonstrate that iHPCs can replicate the yolk-sac-derived fate of human microglia. We transplanted iHPCs, CD34+ hematopoietic progenitor cells, and umbilical cord blood (UCB)-derived monocytes into murine brains and livers, comparing their differentiation into microglia/macrophages. We found that iHPCs generated more microglia-like cells in the brain compared to CD34+ cells and UCB-derived monocytes, with significant differences in migration and differentiation based on the tissue environment. These findings reveal transcriptional network differences influenced by ontogeny and environment, providing insights for developing microglial-based therapies for CNS disorders.
2026-02-26 | GSE307263 | GEO
Project description:Microglia, the brain-resident macrophages, play key roles in neurodevelopment and aging, including neurogenesis, synaptic pruning, and myelination. Dysregulated microglia are implicated in various central nervous system (CNS) disorders. Developing safe microglia replacements and eliminating toxic microglia are promising but challenging approaches for treating CNS diseases. Microglia uniquely originate from primitive yolk-sac hematopoiesis, unlike other tissue-resident macrophages that arise from the postnatal bone marrow. Previous studies show that peripheral macrophages fail to adopt microglial characteristics after transplantation. We aim to understand the transcriptional networks underlying the ontological and environmental differences between microglia and peripheral macrophages, which may guide therapeutic strategies. Using human stem cell-derived hematopoietic progenitors (iHPCs) in a humanized mouse model deficient in resident microglia, we demonstrate that iHPCs can replicate the yolk-sac-derived fate of human microglia. We transplanted iHPCs, CD34+ hematopoietic progenitor cells, and umbilical cord blood (UCB)-derived monocytes into murine brains and livers, comparing their differentiation into microglia/macrophages. We found that iHPCs generated more microglia-like cells in the brain compared to CD34+ cells and UCB-derived monocytes, with significant differences in migration and differentiation based on the tissue environment. These findings reveal transcriptional network differences influenced by ontogeny and environment, providing insights for developing microglial-based therapies for CNS disorders.
2026-02-26 | GSE307262 | GEO
Project description:Microglia, the brain-resident macrophages, play key roles in neurodevelopment and aging, including neurogenesis, synaptic pruning, and myelination. Dysregulated microglia are implicated in various central nervous system (CNS) disorders. Developing safe microglia replacements and eliminating toxic microglia are promising but challenging approaches for treating CNS diseases. Microglia uniquely originate from primitive yolk-sac hematopoiesis, unlike other tissue-resident macrophages that arise from the postnatal bone marrow. Previous studies show that peripheral macrophages fail to adopt microglial characteristics after transplantation. We aim to understand the transcriptional networks underlying the ontological and environmental differences between microglia and peripheral macrophages, which may guide therapeutic strategies. Using human stem cell-derived hematopoietic progenitors (iHPCs) in a humanized mouse model deficient in resident microglia, we demonstrate that iHPCs can replicate the yolk-sac-derived fate of human microglia. We transplanted iHPCs, CD34+ hematopoietic progenitor cells, and umbilical cord blood (UCB)-derived monocytes into murine brains and livers, comparing their differentiation into microglia/macrophages. We found that iHPCs generated more microglia-like cells in the brain compared to CD34+ cells and UCB-derived monocytes, with significant differences in migration and differentiation based on the tissue environment. These findings reveal transcriptional network differences influenced by ontogeny and environment, providing insights for developing microglial-based therapies for CNS disorders.
2026-02-26 | GSE299717 | GEO
Project description:Monocytes populate tissues when local niches are depleted of tissue-resident macrophages, yet the tissue-derived signals controlling monocyte-to-macrophage differentiation are largely undefined. Here, we discovered that the oxysterol receptor GPR183 enables monocytes to sense metabolic niche signals that induce lung macrophage differentiation. We found that interstitial macrophages that continuously turn over express the oxysterol receptor GPR183, whereas alveolar macrophages that derive from embryonic progenitors and slowly turn over did not. Models of conditional tissue-resident macrophage depletion showed that newcomer monocyte-derived macrophages expressed GPR183 along their differentiation trajectory. Recruited GPR183+ monocytes interacted with fibroblasts and lack of GPR183 caused defective lung macrophage differentiation. Single-cell RNA analysis over time identified lung fibroblasts as the source of the GPR183 ligand 7a,25-dihydroxycholesterol in the empty niche. Our findings identify oxysterols as key instructive signals for tissue-resident macrophage development from monocytes.
2026-02-05 | GSE303395 | GEO
Project description:Although classified as hematopoietic cells, tissue-resident macrophages are selfrenewing and maintained independently of adult hematopoiesis. While most macrophages originate from embryonic precursors that seed tissues prior to birth, their exact origin is unknown. Using an in utero macrophage depletion strategy and fatemapping of yolk sac (YS) and fetal liver (FL) hematopoiesis, we found that YS macrophages are the main precursors of microglia, while most other macrophages derive from fetal monocytes. Both YS macrophages and fetal monocytes arise from erythro-myeloid progenitors (EMP) generated in the YS. In the YS, EMP gave rise to macrophages without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal monocytes that then seed embryonic tissues to differentiate into macrophages. Thus, adult tissue-resident macrophages established from HSC-independent embryonic precursors arise from two different developmental programs.
2015-04-23 | GSE66970 | GEO