A Cre-deleter Specific for Embryo-derived Brain Macrophages Reveals Distinct Features of Microglia and Border Macrophages

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Feb 15

PMID 36791722

Authors

Simone Brioschi

Julia A Belk

Vincent Peng

Martina Molgora

Patrick Fernandes Rodrigues

Khai M Nguyen

Shoutang Wang

Siling Du

Wei-Le Wang

Gary E Grajales-Reyes

Jennifer M Ponce

Carla M Yuede

Qingyun Li

John M Baer

David G DeNardo

Susan Gilfillan

Marina Cella

Ansuman T Satpathy

Marco Colonna

Affiliations

Soon will be listed here.

Abstract

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription factor SMAD4 in microglia and embryonic-derived BAMs using Crybb1-Cre caused a developmental arrest of microglia, which instead acquired a BAM specification signature. By contrast, the development of genuine BAMs remained unaffected. Our results reveal that SMAD4 drives a transcriptional and epigenetic program that is indispensable for the commitment of brain macrophages to the microglia fate and highlight Crybb1-Cre as a tool for targeting embryonic brain macrophages.

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