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Developmental Apoptosis Promotes a Disease-Related Gene Signature and Independence from CSF1R Signaling in Retinal Microglia.

Abstract：

:Microglia have important remodeling functions in neurodevelopment, aging, and disease, with evidence for molecular diversity. However, the signaling pathways and environmental cues that drive diverse states of microglia are incompletely understood. We profiled microglia of a discrete developing CNS region, the murine retina. We found distinct transcriptional signatures for retinal microglia across development and peak postnatal density of a population that resembles aging and disease-associated microglia (DAM) and CD11c+ microglia of developing white matter. While TREM2 signaling modulates the expression of select genes, the DAM-related signature is significantly reduced in retinas lacking Bax, a proapoptotic factor required for neuronal death. Furthermore, we found postnatal retinal microglia highly expressing CD11c are resistant to loss or inhibition of colony stimulating factor 1 receptor (CSF1R), while most microglia can be eliminated in Bax knockout retina. Thus, developmental apoptosis promotes a microglia gene signature linked to CSF1R independence that shares features with microglia in developing white matter and in disease.

journal_name

Cell Rep

journal_title

Cell reports

authors

Anderson SR,Roberts JM,Zhang J,Steele MR,Romero CO,Bosco A,Vetter ML

doi

10.1016/j.celrep.2019.04.062

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

2002-2013.e5

issue

7

issn

2211-1247

pii

S2211-1247(19)30535-2

journal_volume

27

pub_type

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