iiinova — where your digital self keeps evolving

Mike Dolan @dolanmjg.bsky.social · 03/05/2025

Delighted to give a talk at the wonderful Cambridge Center for Myelin Repair annual symposium in Cambridge, UK. Truly fantastic conference and an amazing community. Thank you to Thora Karadottir and @mssocietyuk.bsky.social for organising!

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

None of this work would be possible without the mentorship of @bethstevenslab.bsky.social and Evan Macosko. Or the hard work of two phenomenal RAs: @raphaelrakosi.bsky.social and Eric Garcia! Thank you to all our collaborators and coauthors!

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

8/ Summary: Remyelination depends on a glial-immune axis, initiated by type I interferon signaling that summons lymphocytes. Surprisingly, these cytotoxic CD8 T-cells enhance remyelination. Full story ➡️ www.biorxiv.org/content/10.1...

biorxiv.org

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

7/ Critically, depleting the most abundant of these lymphocytes — CD8 T-cells — led to reduced oligodendrocyte maturation, directly linking lymphocyte infiltration to successful remyelination. This was surprising, we expected CD8 T-cells to exert a negative effect on the brain

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

6/ What’s the function of IRG? We demonstrate that IRG secrete CXCL10, a chemokine that recruits lymphocytes into the repairing white matter. Without this glial-driven recruitment, lymphocyte infiltration was impaired.

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

5/ Third, we discovered a shared interferon-response program across multiple glial types. These interferon-responsive glia (IRG) clustered around remyelinating white matter — and their formation was dependent on type I interferon signaling.

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

4/ Second, we observed a selective infiltration of immune cells specifically during remyelination: ➡️ CD8 T-cells ➡️ Natural killer (NK) cells These lymphocytes were specifically enriched during the repair phase, not just during damage.

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

3/ First, glial and monocyte-derived macrophage states are highly dynamic. We found extensive transcriptional remodeling across microglia, astrocytes, and oligodendrocyte lineage cells from demyelination through to repair.

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

2/ We used a focal demyelination model to study the entire process of white matter injury and repair at high spatial and molecular resolution. Our goal: capture the real-time cellular and molecular dynamics driving remyelination.

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Mike Dolan @dolanmjg.bsky.social · 28/04/2025

How does the brain repair myelin after injury? We mapped the full cellular choreography of white matter repair using snRNA-seq + Slide-seqv2, uncovering a type I interferon-driven glial program that recruits lymphocytes to promote remyelination. www.biorxiv.org/content/10.1... Details below 👇

biorxiv.org

Spatiotemporal Analysis of Remyelination Reveals a Concerted Interferon-Responsive Glial State That Coordinates Immune Infiltration

Remyelination, the process by which axons are re-encased in myelin after injury, is a critical step in restoring brain function, yet the dynamics from initial injury to repair remain poorly characteri...

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Reposted by Mike Dolan

Melissa Cooper, PhD @melcooperphd.bsky.social · 16/04/2025

Imaging these astrocytes on the surface of cleared brains was a blast!

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