Making Sure Microglia Are Microglia
If
you use an in vitro model
of microglia and human disease, you need that model to reflect what you see in
vivo.
Microglia can be derived from hiPSCs,
though the process is long and tough. But a new process could change that. This
new work rapidly dervies microglia from monocytes. And
the validation data looks great. Want to see just how much these microglia are
like microglia?
Making Sure Microglia Are Microglia
By
Alomone Team • December 2023
Microglial
dysfunction is a factor in neurological disorders like schizophrenia and
Alzheimer’s disease. To better understand any pathological contribution of
microglia, you need a model that mimics what you see in humans. Currently,
these models may come from human induced pluripotent stem cell(hiPSC)-derived
microglia. But differentiating hiPSCs
into microglia is challenging and often slow, making them unsuitable for high
throughput clinical trials. There’s also the issue that induced microglia (iMGs)
don’t always behave like microglia do in
vivo.
However, new
work has generated iMGs
from monocytes and validated these immunologically, behaviorally, and
genetically. The iMGs
were generated in under two weeks; a significant reduction from the 40 days it
often takes to derive microglia from hiPSCs.
The resulting iMGs
could have real potential in understanding neurological diseases, such as
schizophrenia and Alzheimer’s disease (AD).
Microglia
that look like microglia
The
first step in validating these iMGs
was assessing their morphology. Under phase-contrast, iMGs
started branching at day 5, and by day 10–14 they looked like typical resting
microglia do, with a small cell soma and multiple branches. Induced macrophages
(iMacs) also had the typical “fried-egg” shape with enlarged circular cell
bodies.
Turning
their attention to microglia-specific markers, the researchers looked at
transmembrane protein 119 (TMEM119) and purinergic receptor P2RY12. These are
deemed unique microglia markers but are absent from macrophages. Using
anti-TMEM119 and Alomone’s
Anti-P2Y12 Receptor (extracellular) antibody (#APR-020),
it was clear that TMEM119 and P2RY12 markers were expressed by iMG
cells but absent from iMacs (Figure 1) as expected. This nicely illustrates how
TMEM119 and P2RY12 can be used to distinguish iMG
cells from monocyte-derived macrophages.
Reagents to help your research
If you are interested in studying microglia, we have several reagents that could help.
