Chinese scientists decipher origins of repopulated microglia in brain and retina

March 1, 2018, Chinese Academy of Sciences
Credit: CC0 Public Domain

The regenerative capability of the central nervous system (CNS) is largely limited due to its intrinsic properties and external environment. Traditional thinking holds that once the brain is injured, it is impossible to repair and restore the tissue to normal. However, this notion has been challenged by a recent study.

Microglia are long-lived in the central nervous system (CNS). Elmore and Green et al. reported newly discovered microglial progenitor in Neuron in 2014. This finding showed for the first time microglial progenitors in the adult brain, providing potential insights for . However, the origin of repopulated microglia is still hotly debated, and the source of repopulated microglia remains highly controversial.

Recently, a research paper entitled "Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion" was published in Nature Neuroscience by the laboratory of Bo Peng at the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences. In this paper, PENG and his colleagues successfully deciphered the origin of repopulated microglia in the brain by a series of fate mapping approaches.

Researchers first excluded the blood origin of repopulated microglia via parabiosis, a surgical approach generating chimeric mice with exchanged blood cells (Figure 1a). They then demonstrated that repopulated microglia were NOT differentiated from Nestin-positive progenitor cells (Figure 1b).

They also proved that astrocytes, oligodendrocyte precursor cells (OPCs) and neurons were not the precursor cells of repopulated microglia (Figure 1c). In contrast, ALL repopulated microglia in the brain were derived from the proliferation of the few microglia surviving after pharmacological ablation (<1%), and the dividing microglia transiently expressed Nestin (Figure 1d).

The results provided solid evidence that repopulated microglia were solely derived from residual microglia rather than de novo progenitors, indicating the absence of microglial progenitor cells in the adult brain. In addition, through RNA sequencing, researchers found that the repopulated microglia may share similar functions as the resident microglia in homeostatic and diseased brains.

Moreover, the retina is an important part of the CNS. The capacity for cell regeneration is even more limited in the adult mammalian retina than in the brain. Although a few cells are sporadically regenerated in the retina, no massive cell regeneration had previously been observed.

In a paper entitled "Dual extra-retinal origins of microglia in the model of retinal microglia repopulation" published in Cell Discovery, PENG and his colleagues found that inhibition of CSF1R eliminated all resident microglia in the retina (100%) (Figure 2), in contrast with 99% of the brain.

If the retina shares a similar mechanism for microglia repopulation as that of the (Figure 1), newborn microglia will not emerge and repopulate the retina since there are no surviving microglia after depletion (Figure 2). However, the authors found that new microglia emerged and rapidly repopulated the whole retina after removal of CSF1R inhibition (Figure 2). This is the first time robust and massive cell regeneration has been observed in the adult mammalian retina. And the origin of the retinal microglia is a mystery.

The authors then investigated the origin of repopulated retinal microglia and found that repopulated retinal microglia have two populations of distinct origin: the majority, which are center-emerging microglia; and the minority, which are periphery-emerging microglia.Center-emerging microglia were solely derived from residual microglia in the optic nerve, whereas periphery-emerging microglia were derived from macrophages in the ciliary body/iris (Figure 3).

Through the microglial repopulation model, the authors for the first time observed robust and massive cell regeneration in the adult mammalian retina. Furthermore, they first identified the extra-retinal origin of microglia in the adult retina, shedding new light on the origins and maintenance of in the retina.

These studies were mainly conducted by the laboratory of Bo Peng in collaboration with Dr. Yanxia Rao at the University of Hong Kong and Prof. Ti-Fei Yuan at Shanghai Jiao Tong University. Dr. Yubin Huang and Dr. Zhen Xu are the co-first authors of these two studies.

Explore further: Brain immune system is key to recovery from motor neuron degeneration

More information: Yubin Huang et al, Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0090-8

Related Stories

Brain immune system is key to recovery from motor neuron degeneration

February 20, 2018
The selective demise of motor neurons is the hallmark of Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS). Yet neurologists have suspected there are other types of brain cells involved in the progression ...

New model may provide insights on neurocognitive disorders caused by HIV

November 8, 2017
HIV infects certain cells in the brain called microglia, and infected microglia release toxic and inflammatory molecules that can impair or kill surrounding neurons. Researchers have been limited in their ability to study ...

'Housekeepers' of the brain renew themselves more quickly than first thought

January 10, 2017
A study, led by the University of Southampton and published in Cell Reports, shows that the turnover of the cells, called Microglia, is 10 times faster, allowing the whole population of Microglia cells to be renewed several ...

Brain defense cells live longer than expected

August 29, 2017
Eliminating pathogens and cellular waste is an important task of microglia, the immune cells of the brain. They are among the group of non-neural brain cells that support the normal function of nerve cells. A new study now ...

Skin stem cells used to generate new brain cells

April 25, 2017
Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving ...

Team announces robust, high-throughput protocol for deriving microglia from human stem cells

May 18, 2017
Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly ...

Recommended for you

New technique helps uncover changes in ALS neurons

June 22, 2018
Northwestern Medicine scientists have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells, according to a study ...

Watching stem cells repair spinal cord in real time

June 22, 2018
Monash University researchers have restored movement and regenerated nerves using stem cells in zebra fish where the spinal cord is severely damaged.

Broken shuttle may interfere with learning in major brain disorders

June 22, 2018
Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia, and autism.

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.