@PoratShliomLab

Congrats, Ivy!

Congratulations, Ivy!!

Milestones is an annual publication covering the exciting research performed at the National Cancer Institute, NIH. This year, my group is honored to be included!

Thank you @ivyxiong.bsky.social for being part of the team!

We also host a microscopy database on FocalPlane, which you can use for searching for collaborators, reviewers and speakers.

We'd like to invite all members of the community to join and use the Network.
focalplane.biologists.com/network/

Single cell spatial proteomics maps human liver zonation patterns and their vulnerability to fibrosis https://www.biorxiv.org/content/10.1101/2025.04.13.648568v1

Preprint alert ‼️

Excited to share our work investigating liver zonation in human health and disease with our advanced single-cell Deep Visual Peoteomics framework!

Is liver zonation conserved from mice to humans? And how does fibrosis affect zonation in patients? Now, these questions are answered using scDVP. Some collaborations are meant to be! @carolineweiss.bsky.social@frosenberger.bsky.social @mannlab.bsky.social@mlsb-borgwardt.bsky.social

Check out this preprint from collaborator Lance Johnson @johnsonlab.bsky.social and team characterizing the APOE3 vs E4 #LipidDroplet -ome! Some interesting Easter eggs in there 🐇🥚😉

Very cool!

Thank you, Jonny!

Beautiful work - I love the analysis of organelle rearrangement in response to changes in lipid flux.

Thank you!

Fits nicely with what you showed in brown adipose.

Thank you, Marc!

Thank you, Doug!

Wow!! Amazing preprint from the Porat-Shliom lab showing how organelle signatures vary across space and diet in the liver. This paper has it all: gorgeous microscopy, lipid droplets, mitochondria, and one of my favorite proteins, PLIN5 🤩

Thank you, Sarah! Your insights into PLIN5 functions were invaluable!

Spatially resolved rewiring of mitochondria-lipid droplet interactions in hepatic lipid homeostasis. https://www.biorxiv.org/content/10.1101/2024.12.10.627730v1

Fantastic teamwork in the Porat-Shliom lab AND the amazing resources at the IRP at NCI!

10. In WD conditions, increasing PLIN5 levels enables hepatocytes to regulate the proportion of mitochondria bound to LDs versus those free in the cytosol, facilitating more efficient management of lipid overload.

9. This could explain how, under nutritional deficits, mito simultaneously supports lipid oxidation for ketogenesis while promoting TG synthesis and storage to mitigate lipotoxicity. READ ON...

8. During nutritional stress like fasting, the spatial division is lost, in part due to the upregulation of PLIN5 and its phosphorylation status, leading to the emergence of both types of mitochondria in most hepatocytes. READ ON...

7. Our model: in homeostasis, two types of mitochondria operate simultaneously: periportal mitochondria with a round morphology and a preference for fatty acid oxidation and pericentral mitochondria that synthesize TGs and store them through contact with LDs. more coming...

6. Can introducing mito-LD contacts in WD reduce toxicity? YES! OE of PLIN5 increased mito-LD interactions, improved redox status, and reduced steatosis—highlighting the physiological significance of organelle interactions in lipid homeostasis and tissue health.

5. How do mito-LD contacts regulate lipids? we overexpressed PLIN5 variants in vivo (thanks to @cohenlaboratory.bsky.social for the constructs). We found that 1. PLIN5-induced mito-LD contacts are phosphorylation-dependent. 2. Mito-LD contacts promote expansion and triglyceride synthesis

4. We performed spatial proteomics on sorted hepatocytes to identify the proteins that mediate mitochondria-LD contacts. Many of these proteins are upregulated by fasting, with PLIN5 at the top of the list.

3. One of the significant phenotypes we observed was in fasted mice, where mitochondria-LD contacts were abundant throughout the lobule. In WD-fed mice, however, those interactions were rare.

2. Check out how organelle features change across space and diet! This is just like gene expression signatures! Plus, it can be used for hepatocyte clustering in PCA 😎😎😎

1. We discovered that the spatial positioning of hepatocytes and dietary intervention influenced mitochondrial and LD features. This supports the notion that organelle features encode signatures of zonation and can provide insights into the metabolic state of hepatocytes.