Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages

ABSTRACT: Genetic tools to target microglia specifically and efficiently from the early stages of the embryonic development are missing. Here we present Crybb1-Cre, a new constitutive Cre deleter producing a nearly complete recombination of embryonic brain macrophages (microglia and embryonic BAMs) by the perinatal period, with limited recombination leakage in peripheral myeloid cells. Using this tool, in combination with Flt3-Cre lineage tracer, scRNA-seq analysis and confocal imaging we were able to accurately fate-map embryonic derived versus monocyte derived BAMs in the mouse cortex and identified specific surface markers to resolve either population. Furthermore, we used Crybb1-Cre to delete the transcription factor SMAD4. Using multiomics analysis combining single-cell RNA-seq and ATAC-seq we showed that SMAD4-deficient microglia underwent an arrest of their homeostatic maturation and at the same time acquired a BAMs specification signature. By contrast, BAMs development was unaffected. Therefore, SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate. This data provides a valuable resource to study molecular underpinnings of microglia development.

ORGANISM(S): Mus musculus

PROVIDER: GSE213020 | GEO | 2023/02/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages

Project description:A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages

| PRJNA878792 | ENA

Early fate defines microglia and non-parenchymal brain macrophage development

Project description:Central nervous system (CNS) macrophages comprise parenchymal microglia and border-associated macrophages (BAMs) residing in the meninges, the choroid plexus and the perivascular spaces. With the exception of choroid plexus macrophages, most CNS macrophages emerge during primitive hematopoiesis in the extra-embryonic yolk sac. What remains unknown however, is whether microglia and BAMs share a developmental program or arise from separate predefined lineages. Here, we identified two phenotypically, transcriptionally and locally distinct brain macrophage populations throughout development, giving rise to microglia and BAMs. Two independent macrophage populations were already present in the yolk sac prior to their seeding of the brain. Using fate-mapping system, we demonstrate that in contrast to microglia, the pool of embryonic BAMs in the choroid plexus and the meninges was gradually replaced by precursors emerging later in embryogenesis. The development of microglia was dependent on TGF-β whereas the genesis and maturation of BAMs occurred independently of this cytokine. Collectively, our data show that developing parenchymal and non-parenchymal brain macrophages are separate entities in terms of ontogeny, gene expression signatures and requirement for TGF-β.

2020-04-15 | GSE146926 | GEO

Early fate defines microglia and non-parenchymal brain macrophage development

2020-04-16 | GSE146928 | GEO

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Project description:Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis.

2021-06-20 | GSE178498 | GEO

Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation

Project description:Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells with important homeostatic functions. However, their fate during and after severe episodes of brain inflammation and their relation to recruited monocyte-derived cells remain poorly understood. Here, we show that Trypanosoma brucei parasites invade the brain via its border regions, triggering a disruption of brain barriers and the recruitment of large numbers of monocytes. Fate-mapping combined with single-cell sequencing revealed the remarkable dynamics of resident macrophages, including microglia accumulation around the ventricular ependyma and an expansion of epiplexus cells. Resident macrophages were important for attracting peripheral immune cells and driving a pro-inflammatory response. However, recruited monocyte-derived macrophages reached higher cell densities and exhibited more transcriptional plasticity, adopting anti-microbial gene expression profiles not observed resident macrophages. Remarkably, recruited macrophages were short-lived and rapidly removed upon disease resolution, while activated resident macrophages progressively reverted towards a homeostatic state. Long-term transcriptional alterations were limited for microglia but more pronounced in BAMs. Together our results reveal the diverging responses and dynamics of resident and recruited macrophages upon Trypanosome invasion of the brain.

2022-08-26 | GSE212078 | GEO

A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. [scRNA-Seq]

Project description:While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain.

2019-03-27 | GSE128854 | GEO

A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. [bulk RNA-Seq]

2019-03-27 | GSE128781 | GEO

Gene expression profiling of Myf5-Cre;Smad4flox/flox mouse models of tongue development

Project description:We investigated Smad4-mediated TGF-beta signaling in the development of occipital somite-derived myogenic progenitors during tongue morphogenesis by comparing the transcriptomes of tongue derived from Myf5-Cre;Smad4flox/flox mutant and Myf5-Cre;Smad4flox/+ control mice at day E13.5. Based on gene expression profiles and functional studies, we elucidated the influences Smad4 activity and TGF-beta signaling have on the gene expression profiles underlying tongue development. The data are consistent with the hypothesis that TGF-beta-Smad4-FGF6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis. We obtained RNA samples from tongue tissues of mutant and control mouse embryos (C57BL/6J) at day E13.5 RNA and subjected them to analysis on Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.

2012-02-03 | E-GEOD-35357 | biostudies-arrayexpress

An overlooked subset of Cx3cr1wt/wt microglia in the Cx3cr1CreER-Eyfp/wt mouse has a repopulation advantage over Cx3cr1CreER-Eyfp/wt microglia following microglial depletion

Project description:Cx3cr1CreER-Eyfp/wt mice contain a subset of microglia lacking Cre and EYFP expression. These microglial escape Cre-mediated recombination and gain a repopulation advantage following Cre-driven DTA-mediated microglial depletion.

2022-02-01 | GSE186700 | GEO

Gene expression profiling of Myf5-Cre;Smad4flox/flox mouse models of tongue development

2012-02-03 | GSE35357 | GEO