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Maximilian Heeg @maximilian.heeg.io · Jan 31

📢 Join our team at @alleninstitute.bsky.social! We're hiring a Bioinformatics Scientist II for spatial transcriptomics in immunology.
Our latest work in Nature shows how tissue architecture shapes immune cell diversity. Now we're expanding our team!
Learn more: alleninstitute.org/careers/jobs...

Jobs

alleninstitute.org

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Maximilian Heeg @maximilian.heeg.io · Jan 29

Yes. The colors in the final row are unrelated. This shows Leiden Cluster and not cell types.

Maximilian Heeg @maximilian.heeg.io · Jan 29

The first three rows of Fig 1d are colored as indicated in the legend. Row 4 highlights the antigen specific T cells and row 5 is coloured by leiden clustering. If you want to explore the cell types I recommend having a look at the anndata object: www.ncbi.nlm.nih.gov/geo/query/ac...

Maximilian Heeg @maximilian.heeg.io · Jan 24

Thanks. Are you going to be in asilomar this weekend?

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted - Nature

Maximilian Heeg @maximilian.heeg.io · Jan 23

I cannot believe you still have that picture! That's when all the fun started almost two years ago....

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Reposted by Maximilian Heeg

Eric Topol @erictopol.bsky.social · Jan 22

Spatial omics rides again, this time determining how immune CD8 T cells by location in the gut have different roles, such as killing function in the villus and backup reinforcements in the crypts
www.nature.com/articles/s41...
Good Explainer www.lji.org/news-events/...
@alleninstitute.bsky.social

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Reposted by Maximilian Heeg

Journal of Experimental Medicine @jem.org · Jan 22

New: Amir Ferry, Ananda Goldrath and colleagues @ucsdhealthsci.bsky.social show that differentiation of tissue-resident memory T cells (TRM) is accompanied by the upregulation of the conventional DC1 (cDC1) chemoattractant, Xcl1. https://buff.ly/4hrKCYe

#MucosalImmunology #TumorImmunology

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Reposted by Maximilian Heeg

Allen Institute @alleninstitute.org · Jan 22

When your gut is under attack, the immune system is activated. Like any good army, the roles of each cellular soldier depends on their location. 🧵

📸 Elena Lin/ @ucsdhealthsci.bsky.social

#ImmunoSky

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Maximilian Heeg @maximilian.heeg.io · Jan 22

Beautiful thread on how tissue-resident T cells organize in the gut post-infection from my co-conspirator @reinacampos.bsky.social. Our spatial multi-omics work revealed unexpected complexity in immune system architecture. Think less checkers, more 4D chess 🧬🔬

Miguel Reina-Campos @reinacampos.bsky.social · Jan 22

It turns out the immune system is playing 4D chess while we thought it was just playing checkers. Using #spatialtranscriptomics from @10xgenomics.bsky.social and @vizgen.bsky.social we were able to peek into the secret lives of tissue resident T cells in the gut as they form after infection 1/n

Profiling of the location and transcriptome of tissue-resident memory CD8 T cell formation at single-transcript resolution finds regionalized signalling as the basis of immune diversity in t...

T cells rise up to fight infections in the gut

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Reposted by Maximilian Heeg

La Jolla Institute for Immunology (LJI) @lji.org · Jan 22

New in @nature.com — LJI's @reinacampos.bsky.social and colleagues at @ucsdhealthsci.bsky.social and @alleninstitute.bsky.social track the amazing journey of T cells in the gut.

“For the first time, we were able to capture the formation of immunological memory in space and time."

bit.ly/40Tnlt7

Scientists show how a special group of T cells travels through the small intestine to combat pathogens

www.lji.org

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Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 10/10 This work establishes a framework for studying tissue immune networks and reveals how cellular positioning shapes immune cell identity and function. Full paper: www.nature.com/articles/s41...
Big thanks again to all the authors for their incredible work! ❤️

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted - Nature

Profiling of the location and transcriptome of tissue-resident memory CD8 T cell formation at single-transcript resolution finds regionalized signalling as the basis of immune diversity in t...

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Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 9/10 Technical innovation: We developed a strategy for pooled optically encoded gene perturbations compatible with spatial transcriptomics, enabling mechanistic studies in situ

Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 8/10 Our spatial framework reveals that T cell location and functional state are fundamentally intertwined - establishing a new paradigm for understanding tissue immunity

Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 7/10 Importantly, we validated these findings in human tissue. Analysis of healthy human terminal ileum revealed similar spatial organization of CD8 T cell states

Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 6/10 TGFβ signaling proved essential for proper TRM positioning. TGFβRII KO cells showed impaired migration to the villus tip and reduced acquisition of tissue-residency programs

Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 5/10 Using CRISPR-based perturbations with spatial readout, we demonstrated that CXCR3 signaling is crucial for early positioning of effector cells. Loss of CXCR3 altered cellular positioning and subsequent differentiation fate

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Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 4/10 This diversity is regulated by:
1. Distinct ligand-receptor activities
2. Spatial cytokine gradients
3. Specialized cellular contacts creating a complex molecular landscape that guides TRM differentiation

Specialized cellular contacts create a complex molecular landscape that guides TRM differentiation. Cells in the small intestine are colored by cell type and connected to their neighboring cells.

Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 3/10 Key finding: We identified two distinct TRM states defined by their location:
• Differentiated TRM cells (Gzma+, Gzmb+, Itgae+) in upper villus
• Progenitor-like TRM cells (Tcf7+, Slamf6+) in lower villus/crypt

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Maximilian Heeg @maximilian.heeg.io · Jan 22

🧵 2/10 Using spatial transcriptomics (Xenium & MERSCOPE), we discovered that intestinal TRM cells occupy distinct niches that shape their phenotype and function. We developed computational approaches to map cells along three anatomical axes 📊

Each cell is colored according to its positions along the 3 main axes (crypt to villus, epithelial distance and longitudinal).

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted - Nature

Maximilian Heeg @maximilian.heeg.io · Jan 22

Today in @nature.com. We mapped the spatial and temporal dynamics of intestinal tissue-resident memory CD8 T (TRM) cell differentiation.
🔗 www.nature.com/articles/s41....
@ucsandiego.bsky.social @lji.org @alleninstitute.bsky.social @amonell.bsky.social @reinacampos.bsky.social @GoldrathLab 🧵 1/10

Profiling of the location and transcriptome of tissue-resident memory CD8 T cell formation at single-transcript resolution finds regionalized signalling as the basis of immune diversity in t...