gabrielmckinsey.bsky.social
Neuroimmunologist and developmental biologist at the University of California San Francisco Department of Pediatrics.
Google scholar: https://scholar.google.com/citations?user=ZaUcPIkAAAAJ&hl=en
117 posts
2,108 followers
1,300 following
Regular Contributor
Active Commenter
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Nice! Have a fun and safe drive!
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Yeah, this hapoens at UCSF, but I believe you can get an extension. Or at least that was an option for me in the past. Congrats on the move! Good luck!
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This is a great idea. I hope it makes it to the floor quickly.
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Gorgeous!
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Thanks Julie! Yeah, these interactions in the meninges are super interesting! I’m really interested in looking at macrophage developmental state changes in this niche, and how this relates to their positioning and physical interactions with other cells
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Heya! Great to see you here!
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Finally, I would like to note that I’m on the faculty job market! Please feel free to reach out about my work or if you know of any openings that might be a good fit. In this chaotic time, let's do our best to support and protect the most vulnerable! Good luck and stay safe everyone! (21/21)
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Phew! If you've followed the thread to the end, thanks for sticking it out! Congrats to everyone involved, particularly Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Dean Sheppard, Oleg Butovsky, and Tom Arnold. A ton of work went into this study! (20/21)
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Their findings are complementary with ours, supporting the conclusions of our respective manuscripts. Here’s a link to their work: www.nature.com/articles/s41.... (19/21)
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I would also like to note that, while our manuscript was under review, another study by our collaborators Bedolla et al. was published regarding the role of Tgfb1 in the maintenance of adult microglial homeostasis. (18/21)
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characterized by widespread loss of P2RY12 expression, but restricted upregulation of reactive markers in the white matter, suggesting that microglia in some brain regions or niches are more sensitive to disruption in canonical Tgfb signaling. (17/21)
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We suggest that this may be due to the contribution of non-canonical Tgfb signaling disruption in the more “upstream” cKO models that disrupt Tgfb signaling. Interestingly, there were interesting regional differences in the microglial changes in the Smad2/3 cKO model… (16/21)
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In a cross comparison of a variety of genetic models where Tgfb signaling is disrupted in microglia, we found that cKO of the downstream mediators of Tgfb signaling Smad2/3 resulted in less profound neurological disruption, and a correspondingly less severe neuroinflammatory phenotype. (15/21)
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We believe this may be due to the rescue of Tgfb1 signaling in the endothelia by Tgfb1 expression in pericytes. (14/21)
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In a separate series of experiments, in an attempt to better understand the role of Tgfb1 in blood vessel development, we used a series of cKO experiments to delete Tgfb1 in blood vessels. However, in these mice we did not observe the hemorrhage seen in Tgfb1 null mice. (13/21)
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In these microglial cKO experiments we did not see the pervasive brain hemorrhage found in Tgfb1 null mice, suggesting that avb8-Tgfb1 signaling in microglia vs blood vessels is dissociable. (12/21)
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we see a similar reversion of microglia towards an earlier developmental stage, suggesting that Tgfb1 is necessary for both the acquisition and maintenance of microglial identity. (11/21)
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Using different cKO models to delete Tgfb1 in different myeloid populations, we found that when we deleted Tgfb1 in microglia we completely blocked microglial differentiation, similar to what we saw in Itgb8 cKO mice. When we deleted Tgfb1 during neonatal brain development and in adulthood, …(10/21)
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Which Tgfb ligand regulates microglial development? Tgfb1 has been implicated in microglial development, but previous studies of Tgfb1 null mice found pervasive vascular dysfunction and hemorrhage, complicating the interpretation of the neuroimmune phenotypes in these mice. (9/21)
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We then looked at the epigenetic signature of these developmentally disrupted microglia by ATAC-seq and H3K7ac ChIP-seq. This analysis provided a wealth of data that we are still poring over, particularly regarding the cis-regulatory control of microglial identity. (8/21)
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We found that these developmentally disrupted microglia migrate into the brain, but retain the gene expression patterns of early embryonic immature microglia. Interestingly, these developmentally expressed genes are also upregulated by microglia in the context of brain injury and disease. (7/21)
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specific neurological or behavioral impairments be attributed to chronic developmental neuroinflammation in spatially restricted regions of the brain. (6/21)
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A model of spatially restricted developmental neuroinflammation! By deleting Itgb8 using Cre drivers that recombine progenitors in specific embryonic brain regions, we can interrogate whether… (5/21)
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Remarkably, when microglial differentiation is disrupted via conditional deletion of integrin beta 8 in the progenitors of a particular brain region, this leads to the spatially restricted disruption of microglial differentiation, but only in the brain regions that those progenitors produce! (4/21)
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We show that the processes of radial glia neural progenitors contact immature macrophages in the meninges of the developing embryo. We propose that this physical contact between neural progenitors and immature microglia is necessary for microglial development. (3/21)
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How does the brain drive microglial identity acquisition? Using a systematic series of conditional mutagenesis experiments, we show that the expression of the TGF-beta activating integrin avb8 complex in neural stem cells is necessary for proper microglial differentiation. (2/21)
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Thank you for sharing this!
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Interrogated*
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Yeah, being detained and interogated for political opinions is a clear violation of a person’s 1st amendment rights.
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There was no evidence of material support. The justification is that, as you said above “…some opinions create suspicion of illegal activity.” Which is just utter bs.
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Detaining someone because you disagree with their politics is a clear violation of their 1st amendment rights. This is a particularly clear example of it as he is a popular media persona.
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An absurd argument. Under this logic the government could detain half of the US population. Which is maybe your preference, but not allowed under the US Constitution.
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Freedom of speech and the press is protected under the 1st amendment in the US Constitution. These are among the most important and fundamental rights in the US. The eroding of these rights are part of our country’s current slide toward fascism.
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Joe Rogan has expressed support for Jan 6th rioters. Does that mean that the government has reasonable suspicion to detain and interogate him? See how absurd this argument becomes when reversed?
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Fine, extremely popular Youtuber who does in-depth research and interviews, as a journalist does. The same reasoning applies, and makes him a big target for the administration.
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This isn’t about suspicion, it’s intimidation to suppress free speech, something that this administration is eager to do. There’s no reasonable suspicion to think that this journalist is a terrorist. Simply absurd.
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False equivalence. The Tate brothers have been indicted on *actual evidence* of human trafficking, not because of their opinions. Sheesh.
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Thank you!
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Congrats! Beautiful work!