Similar Datasets
Project description:Purpose: The purpose is to systemically identify RNA expression between skin mast cells with distinct origins. Methods: We profiled RNA-seq in skin mast cells with distinct origins. Results: Early, late EMP and fetal HSC-derived skin mast cells display distinct transcriptome profiles.
2018-10-05 | GSE119016 | GEO
Project description:Purpose: The purpose is to systemically identify RNA expression changes along mast cell development during embryogenesis. Methods: We profiled RNA-seq in early EMPs and their progeny. Results: Fetal MCPs acquire the mast cell-specific gene signature from E11.5 and complete their maturation in peripheral tissues.
2018-10-15 | GSE119017 | GEO
Project description:Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors
| PRJNA487779 | ENA
Project description:Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors [origins]
| PRJNA487777 | ENA
Project description:Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors [development]
| PRJNA487781 | ENA
Project description:Most haematopoietic cells renew from adult haematopoietic stem cells (HSCs), however, macrophages in adult tissues can self-maintain independently of HSCs. Progenitors with macrophage potential in vitro have been described in the yolk sac before emergence of HSCs, and fetal macrophages can develop independently of Myb, a transcription factor required for HSC, and can persist in adult tissues. Nevertheless, the origin of adult macrophages and the qualitative and quantitative contributions of HSC and putative non-HSC-derived progenitors are still unclear. Here we show in mice that the vast majority of adult tissue-resident macrophages in liver (Kupffer cells), brain (microglia), epidermis (Langerhans cells) and lung (alveolar macrophages) originate from a Tie2(+) (also known as Tek) cellular pathway generating Csf1r(+) erythro-myeloid progenitors (EMPs) distinct from HSCs. EMPs develop in the yolk sac at embryonic day (E) 8.5, migrate and colonize the nascent fetal liver before E10.5, and give rise to fetal erythrocytes, macrophages, granulocytes and monocytes until at least E16.5. Subsequently, HSC-derived cells replace erythrocytes, granulocytes and monocytes. Kupffer cells, microglia and Langerhans cells are only marginally replaced in one-year-old mice, whereas alveolar macrophages may be progressively replaced in ageing mice. Our fate-mapping experiments identify, in the fetal liver, a sequence of yolk sac EMP-derived and HSC-derived haematopoiesis, and identify yolk sac EMPs as a common origin for tissue macrophages.
| S-EPMC5997177 | biostudies-literature
Project description:Although classified as hematopoietic cells, tissue-resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth to generate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue-resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs.
| S-EPMC4545768 | biostudies-literature
Project description:The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from haematopoietic precursors.
| S-EPMC6289247 | biostudies-literature
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:The pathophysiology of neurodegenerative diseases is poorly understood and there are few therapeutic options. Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss, and chronic glial activation. Whether microglial activation, which is generally viewed as a secondary process, is harmful or protective in neurodegeneration remains unclear. Late-onset neurodegenerative disease observed in patients with histiocytoses, which are clonal myeloid diseases associated with somatic mutations in the RAS-MEK-ERK pathway such as BRAF(V600E), suggests a possible role of somatic mutations in myeloid cells in neurodegeneration. Yet the expression of BRAF(V600E) in the haematopoietic stem cell lineage causes leukaemic and tumoural diseases but not neurodegenerative disease. Microglia belong to a lineage of adult tissue-resident myeloid cells that develop during organogenesis from yolk-sac erythro-myeloid progenitors (EMPs) distinct from haematopoietic stem cells. We therefore hypothesized that a somatic BRAF(V600E) mutation in the EMP lineage may cause neurodegeneration. Here we show that mosaic expression of BRAF(V600E) in mouse EMPs results in clonal expansion of tissue-resident macrophages and a severe late-onset neurodegenerative disorder. This is associated with accumulation of ERK-activated amoeboid microglia in mice, and is also observed in human patients with histiocytoses. In the mouse model, neurobehavioural signs, astrogliosis, deposition of amyloid precursor protein, synaptic loss and neuronal death were driven by ERK-activated microglia and were preventable by BRAF inhibition. These results identify the fetal precursors of tissue-resident macrophages as a potential cell-of-origin for histiocytoses and demonstrate that a somatic mutation in the EMP lineage in mice can drive late-onset neurodegeneration. Moreover, these data identify activation of the MAP kinase pathway in microglia as a cause of neurodegeneration and this offers opportunities for therapeutic intervention aimed at the prevention of neuronal death in neurodegenerative diseases.
| S-EPMC6047345 | biostudies-literature