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

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

PROVIDER: PRJNA878792 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21508200.fastq.gz	Fastqsanger.gz
	SRR21508201_1.fastq.gz	Fastqsanger.gz
	SRR21508201_2.fastq.gz	Fastqsanger.gz
	SRR21508202.fastq.gz	Fastqsanger.gz
	SRR21508203_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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