Will Aisenberg
@waisenberg.bsky.social
Neuroscientist using microglia replacement to understand the influence of brain macrophages on neurodegenerative disease | postdoc FC Bennett lab @ UPenn | Hopkins Sumner lab and CMM alum
Good morning @gliameeting.bsky.social! Don’t miss @fchrisbennett.bsky.social talk today to hear about what we’re doing with microglia replacement #glia2025
July 9, 2025 at 7:21 AM
Good morning @gliameeting.bsky.social! Don’t miss @fchrisbennett.bsky.social talk today to hear about what we’re doing with microglia replacement #glia2025
Bottom line:
We uncovered distinct microglia dysfunction and showed that CNS-limited microglia replacement improves a monogenic neurodegenerative disease.
This work warrants continued exploration of microglia replacement as a therapeutic strategy!
8/8
We uncovered distinct microglia dysfunction and showed that CNS-limited microglia replacement improves a monogenic neurodegenerative disease.
This work warrants continued exploration of microglia replacement as a therapeutic strategy!
8/8
April 30, 2025 at 3:39 PM
Bottom line:
We uncovered distinct microglia dysfunction and showed that CNS-limited microglia replacement improves a monogenic neurodegenerative disease.
This work warrants continued exploration of microglia replacement as a therapeutic strategy!
8/8
We uncovered distinct microglia dysfunction and showed that CNS-limited microglia replacement improves a monogenic neurodegenerative disease.
This work warrants continued exploration of microglia replacement as a therapeutic strategy!
8/8
The result? 🧠✨
✅ Normalized myeloid transcriptome
✅ Improved neuropathology
✅ Increased survival
7/8
✅ Normalized myeloid transcriptome
✅ Improved neuropathology
✅ Increased survival
7/8
April 30, 2025 at 3:39 PM
The result? 🧠✨
✅ Normalized myeloid transcriptome
✅ Improved neuropathology
✅ Increased survival
7/8
✅ Normalized myeloid transcriptome
✅ Improved neuropathology
✅ Increased survival
7/8
But can replacing microglia modify disease?
Using genetic tools, we depleted brain macrophages in neonatal twitcher mice and replaced them with healthy donor monocytes.
These new cells filled the brain & spinal cord.
6/8
Using genetic tools, we depleted brain macrophages in neonatal twitcher mice and replaced them with healthy donor monocytes.
These new cells filled the brain & spinal cord.
6/8
April 30, 2025 at 3:39 PM
But can replacing microglia modify disease?
Using genetic tools, we depleted brain macrophages in neonatal twitcher mice and replaced them with healthy donor monocytes.
These new cells filled the brain & spinal cord.
6/8
Using genetic tools, we depleted brain macrophages in neonatal twitcher mice and replaced them with healthy donor monocytes.
These new cells filled the brain & spinal cord.
6/8
Among these, we identified a key signature:
✅ GPNMB
✅ MS4A
✅ SPP1
✅ LGALS3
And validated expression of these markers in both mouse and human globoid cells.
5/8
✅ GPNMB
✅ MS4A
✅ SPP1
✅ LGALS3
And validated expression of these markers in both mouse and human globoid cells.
5/8
April 30, 2025 at 3:39 PM
Among these, we identified a key signature:
✅ GPNMB
✅ MS4A
✅ SPP1
✅ LGALS3
And validated expression of these markers in both mouse and human globoid cells.
5/8
✅ GPNMB
✅ MS4A
✅ SPP1
✅ LGALS3
And validated expression of these markers in both mouse and human globoid cells.
5/8
But what about globoid cells?
We found multiple disease-associated myeloid states in our sequencing with overlapping markers—suggesting a spectrum of macrophage states, rather than a single cell type.
4/8
We found multiple disease-associated myeloid states in our sequencing with overlapping markers—suggesting a spectrum of macrophage states, rather than a single cell type.
4/8
April 30, 2025 at 3:39 PM
But what about globoid cells?
We found multiple disease-associated myeloid states in our sequencing with overlapping markers—suggesting a spectrum of macrophage states, rather than a single cell type.
4/8
We found multiple disease-associated myeloid states in our sequencing with overlapping markers—suggesting a spectrum of macrophage states, rather than a single cell type.
4/8
Our sequencing revealed early microglial induction of interferon-stimulated genes (ISGs) in the twitcher mouse model.
When we validated this with in situ hybridization, we saw striking ISG expression patches—increasing in abundance as disease progressed.
3/8
When we validated this with in situ hybridization, we saw striking ISG expression patches—increasing in abundance as disease progressed.
3/8
April 30, 2025 at 3:39 PM
Our sequencing revealed early microglial induction of interferon-stimulated genes (ISGs) in the twitcher mouse model.
When we validated this with in situ hybridization, we saw striking ISG expression patches—increasing in abundance as disease progressed.
3/8
When we validated this with in situ hybridization, we saw striking ISG expression patches—increasing in abundance as disease progressed.
3/8
Krabbe disease features large lipid-laden macrophages. These “globoid cells” were first described over 100 years ago, yet their role in disease remains unclear.
We used scRNA-seq to update the definition of these pathognomonic cells, and track macrophage dysfunction over time.
2/8
We used scRNA-seq to update the definition of these pathognomonic cells, and track macrophage dysfunction over time.
2/8
April 30, 2025 at 3:39 PM
Krabbe disease features large lipid-laden macrophages. These “globoid cells” were first described over 100 years ago, yet their role in disease remains unclear.
We used scRNA-seq to update the definition of these pathognomonic cells, and track macrophage dysfunction over time.
2/8
We used scRNA-seq to update the definition of these pathognomonic cells, and track macrophage dysfunction over time.
2/8
So proud of this work from @kel-nem.bsky.social! She developed a cool new tool to study brain macrophages and their role in disease - using AGS mutations to show mutant macrophages alone can drive a striking interferon response.
January 7, 2025 at 3:42 AM
So proud of this work from @kel-nem.bsky.social! She developed a cool new tool to study brain macrophages and their role in disease - using AGS mutations to show mutant macrophages alone can drive a striking interferon response.
I had an amazing time in cold spring harbor last week. I got to meet new people, learn new science, and gained confidence in my writing ability. I highly recommend the writing retreat if you’re a trainee looking for dedicated time to progress that grant/paper meetings.cshl.edu/courses.aspx...
November 25, 2024 at 1:23 PM
I had an amazing time in cold spring harbor last week. I got to meet new people, learn new science, and gained confidence in my writing ability. I highly recommend the writing retreat if you’re a trainee looking for dedicated time to progress that grant/paper meetings.cshl.edu/courses.aspx...
Or out of the library… 🏖️
November 23, 2024 at 4:23 AM
Or out of the library… 🏖️
November 22, 2024 at 8:22 PM
👋🏻 Hi Bluesky, I’m a postdoc using #microglia replacement to understand the influence of brain macrophages on neurodegenerative disease. Here’s a pretty picture of a brain filled with donor macrophages (🟢) #neuroskyence #glia
November 14, 2024 at 2:02 PM
👋🏻 Hi Bluesky, I’m a postdoc using #microglia replacement to understand the influence of brain macrophages on neurodegenerative disease. Here’s a pretty picture of a brain filled with donor macrophages (🟢) #neuroskyence #glia