A Core Transcription Regulatory Circuitry Defining Microglia Cell Identity Inferred from the Reanalysis of Multiple Human Microglia Differentiation Protocols.

Antoine Aubert,Marco Antonio Mendoza-Parra,François Stüder,Bruno Maria Colombo

doi:10.3390/brainsci11101338

Abstract

Microglia, the immune cells in the brain involved in both homeostasis and injury/infection control, play a predominant role in neurodegenerative diseases. In vivo studies on microglia are limited due to the requirement of surgical intervention, which can lead to the destruction of the tissues. Over the last few years, multiple protocols—presenting a variety of strategies—have described microglia differentiation issued from human pluripotent stem cells. Herein, we have reanalyzed the transcriptomes released on six different microglia differentiation protocols and revealed a consensus core of master transcription regulatory circuitry defining microglia identity. Furthermore, we have discussed the major divergencies among the studied protocols and have provided suggestions to further enhance microglia differentiation assays.

Highlights

Microglia represent about 10% of the cells in the brain. They are localized in the parenchyma and are the most representative immune cells of the central nervous system (CNS) [1]
Comparative Reanalysis of Whole Transcriptome Readouts Generated within Six induced pluripotent stem cell (iPSC)–Derived Microglia Differentiation Studies
TF-overexpression protocol used by Chen andcells colleagues brain, is involved in both homeostasis and injury/infection control and that it plays a targets the factors CEBPA and SPI1, we focused our attention to their corresponding predominant in neurodegenerative diseases

Summary

Introduction

Microglia represent about 10% of the cells in the brain. They are localized in the parenchyma and are the most representative immune cells of the central nervous system (CNS) [1]. Microglia derive during early embryogenesis from yolk sac–primitive macrophages and begin to colonize the brain before the emergence of neurons and macroglia. These primitive myeloid progenitors are highly proliferated throughout embryonic life and constitute the resident adult microglia in a healthy brain. These cells persist during adulthood via constant self-renewal. Postnatal hematopoietic progenitors contribute to the adult microglial pool and are constantly renewed throughout life [2,3,4]

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Results

Conclusion