fifty shades of microglia


Fifty Shades of Microglia.Brioschi S, Peng V, Colonna M. Trends Neurosci. 2019 Apr 17. pii: S0166-2236(19)30044-X.
In a recent study, Masuda and colleagues (Nature 2019;566:388-392) used single-cell RNA-sequencing (scRNA-seq) to profile microglia across different anatomical compartments, developmental stages, and types of brain pathology in mice. Moreover, the authors performed a novel transcriptomic characterization of microglia from multiple sclerosis patients and identified phenotypically conserved microglial subsets between species. These findings, together with seminal prior results from various groups, provide valuable insights into the spatiotemporal heterogeneity of microglia during brain development and disease.

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution.Masuda T, Sankowski R, Staszewski O, Böttcher C, Amann L, Sagar, Scheiwe C, Nessler S, Kunz P, van Loo G, Coenen VA, Reinacher PC, Michel A, Sure U, Gold R, Grün D, Priller J, Stadelmann C, Prinz M. Nature. 2019 Feb;566(7744):388-392

Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system. These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies.

Yesterday someone said microglia why don’t you post on hot microglia imaging. Well we have done this already and now I believe some of those tools are not fit for purpose as they label other stuff in addition to microglia, like astrocytes and otherstructures. However microglia can have many faces

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  • Dear Team G, I have written an op-ed and would like you to publish It, not in the comment section, but in the guest reader format. I hope you will honour my request.
    “Doctors put drugs of which they know little into bodies of which they know less for diseases of which they know nothing at all.”― Voltaire

    I have a question for all of you: is this blog really a platform of good science in the field of multiple sclerosis advancement, or is it a sham?

    Good science by definition allows for more than one opinion, otherwise you have the will of a small clique of pervasive people, which by its very nature forms the basis of a cult. That is what this blog has become: an MS cult.

    Don Giovannoni has effectively brainwashed a very vulnerable group of individuals suffering from multiple sclerosis and, as their cult figurehead, is very forcefully pushing is pro-pharmacological agenda.

    We are living in era where the NHS has become massively weaponised. This is, in my opinion, a heinous reality and the activities of Don Giovannoni have only contributed to its continuing downfall. The risk-sharing schemes propagated by neurologists like him and others during the last few decades has materialised in an NHS where investment and reality do not coalesce. Big pharmaceutical agencies have infiltrated multiple sclerosis healthcare, offering at best mediocre therapies that claim miracles, whereas the multiple sclerosis sufferer’s natural healing biology has arguably done the bulk of their recovery for them, not the expensive neo-DMTs.

    Don Giovannoni has been running this blog for over a decade now and one has to really question whether the landscape of multiple sclerosis agencies is in a better position now then what it was back in the noughties. The reason I argue this point is simply because Don Giovannoni has failed to position his vision to an audience that can fund and elevate his ambition of purloining already decades-old medication and repurposing it for greater profit. The landscape of multiple sclerosis drugs’ therapy ought to now be leagues ahead of where it is currently, but here we are, stuck in a situation where rubbish invented sixty-years ago is being propositioned in order to mask the reality that a neurologist like Don Giovannoni has abjectly failed in succeeding to do his job.

    The things I am arguing here will no doubt antagonise what has become a very loyal cult following who will willingly go down protecting their cult leader – and they very will may do so if these neo-DMTs come up short. Who can blame them? After all, they are desperate for miracles and those behind this blog are more then willing to cater for them. Even now Don Giovannoni cannot certifiably tell you why your MS disease has occurred, yet he has the audacity to push dangerous biological agents that may in the long-term do greater damage than what you can scientifically envisage.

    The in amelioration of multiple sclerosis is a fantasy, heck; the industry cannot even manage symptomatic aspects of the disease convincingly, let alone curative areas.

    In our current age we need to scrutinise those in a position of power and not defer so blindly to their vested will. Both the World Health Organisation and European Medical Agency have obliterated many of Don Giovannoni’s championed ‘miracles’, meaning his pontificated glories are steadily falling by the wayside. This is very much a blog in its decline. The winning-side is not to be found here, my bredrins, as its glory days waned some time ago.

    The future may be bright, but it’s certainly not the Barts and the London.

      • Cult = a system of religious veneration and devotion directed towards a particular figure or object.

        I think not!

    • As one of the brainwashed please enlighten me as to what you see as the alternative to drug therapies? As someone who has never smoked, grew up on a farm, always exercised, eaten almost exclusively unprocessed food that is primary plant based and still has MS I don’t see any real alternative to drugs. It is not Dr Giovannoni’s fault he has not found a cure and I think you have unfair expectations of him and the other neurologists who do their very best for us.

      I like this blog. The fact that they publish your nonsensical diatribe says a great deal about how an openness to contrary views.

      Thank-you Dr. Giovannoni and all the other neurologists who post here! I’m deeply grateful for how much you care.

  • Hi Dr. Dre.

    I agree with some of your points about where we are currently at in the disappointing MS treatment world. No known cause, no remyelination or neurorestoration treatments and no neurodegenerative inhibitors and specifically no meaningful treatment of progressive MS.

    If I hear diagnose and treat early I think my head will explode as what the hell are people with progressive MS that missed the therapeutic window supposed to do? Clearly the immunosuppressive model only has failed to treat progression of MS.

    I however don’t agree with your criticism of Dr. Giovannoni or his team. It seems you have supplanted your hatred of MS with Dr. Giovannoni. It is not his fault we have this dreaded disease. This team has placed itself in a very vulnerable position by being the rare group that gives us valuable insight into the MS research world.

    I think MS Societies are corrupt giving pennies on the dollar to research. I think journals are corrupt when they are funded by pharma. I think steering committees and approving bodies are corrupt. I think the card carrying neurologists are conflicted and could be doing more to help stimulate innovative research instead of supporting recycled old drugs from dermatology, oncology and other medical fields.

    This disease has stolen much from us all but I think your hatred is misplaced as this website provides valuable information both good and bad to us all.

    • Dre you are beginning to sound like Donald Trump. Trump claims that there is a conspiracy theory behind everything.

      I am not convinced this is the real Dre; he/she was infinitely more eloquent than this.

  • Blind Faith – belief without true understanding, perception or discrimination – again – don’t think so!

    No surprise Dr Dre that I’m another who thinks the validity of some of your argument is undermined by an overwhelming element of hostility towards ProfG, conspiracy theory, and by being presented as a tirade.

    Assuming those of us who appreciate this site are most definitely dumb arses, who haven’t even contemplated the value in accessing other information and opinions, let alone actually done so, is as naive and ignorant of you as you’re claiming the readship to be.

  • Dr. Dre you overestimate ProfG and underestimate us patients. You sound quite paternalistic trying to minimize OUR experience in the disease decisions. You also neglect the very important patient movement of HSCT that tries to fight the disease as intensively as possible but out of Pharma norm. And you didn’t even offer some scientific reasoning for your claims.

    You tried to offend ProfG but you managed to offend us patients.

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