The transcription factor PU.1 is critical for viability and function of human brain microglia.

Abstract:

:Microglia are the predominant resident immune cells of the brain and can assume a range of phenotypes. They are critical for normal brain development and function but can also contribute to many disease processes. Although they are widely studied, the transcriptional control of microglial phenotype and activation requires further research. PU.1 is a key myeloid transcription factor expressed by peripheral macrophages and rodent microglia. In this article, we report the presence of PU.1 specifically in microglia of the adult human brain and we examine its functional role in primary human microglia. Using siRNA, we achieved substantial PU.1 protein knock-down in vitro. By assessing a range of characteristic microglial proteins we found decreased viability of adult human microglia with reduced PU.1 protein expression. This observation was confirmed with PU.1 antisense DNA oligonucleotides. An important function of microglia is to clear debris by phagocytosis. We assessed the impact of loss of PU.1 on microglial phagocytosis and show that PU.1 siRNA reduces the ability of adult human microglia to phagocytose amyloid-beta1-42 peptide. These results show that PU.1 controls human microglial viability and function and suggest PU.1 as a molecular target for manipulation of human microglial phenotype.

journal_name

Glia

journal_title

Glia

authors

Smith AM,Gibbons HM,Oldfield RL,Bergin PM,Mee EW,Faull RL,Dragunow M

doi

10.1002/glia.22486

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

929-42

issue

6

eissn

0894-1491

issn

1098-1136

journal_volume

61

pub_type

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