A spatial atlas of the healthy human liver from live donors - Nature A human spatial atlas of gene expression in liver based on live donors shows marked porto–central zonation of hepatocytes and non-parenchymal cells, and transcriptomic changes in early steatosis.

Nature research paper: A spatial atlas of the healthy human liver from live donors
go.nature.com/4mwc6zV

All data and code are available in the preprint, also check out the associated villus zonation browser app to explore your favorite genes in control and Celiac patients' intestinal biopsies: shalevapps.weizmann.ac.il/celiac_atlas/.

Our findings suggest that malabsorption in Celiac Disease stems not only from reduced epithelial surface area, but also from disruption of finely tuned zonal enterocyte identities. Great work by Tal Barkai and our friends at the Schneider Medical Center DrorShouval and Raanan Shamir.

Finally, ~7% of epithelial cells completely lost enterocyte identity and exhibited gastric metaplasia.

We found that this abnormal co-expression arises from spatial overlap of morphogen gradients: BMP signals from the villus tip and WNT signals from the crypt base now intersect due to the reduced distance between their sources.

Surprisingly, in Celiac Disease, enterocytes adopted a new cellular state. Rather than losing specific zones, remaining enterocytes co-expressed gene programs that, in healthy tissue, are restricted to distinct villus zones.

To address this, we applied spatial transcriptomics (VisiumHD) to human small intestinal tissue, together with matched single-cell RNA-seq, to analyze enterocyte zonal identity.
In the healthy pediatric intestine, enterocytes displayed pronounced zonation along the villus axis.

We asked: does villus flattening cause loss of specific zonal populations, proportional scaling of zonation or a breakdown of spatial organization.

Enterocytes exhibit different cellular states depending on their height along the small intestine villus axis, a phenomenon known as ‘zonation’. In Celiac Disease, autoimmune destruction of enterocytes leads to villus flattening.

Happy to share our new preprint: Spatial Rewiring of Enterocyte Identity in Celiac Disease. We describe unexpected changes in enterocyte zonation in Celiac Disease.

With the emergence of VisiumHD and other spatial transcriptomics datasets, HiVis facilitates exploring intra-cellular mRNA localization patterns across tissues and conditions. Great work by Roy Novoselsky and Ofra Golani.

HiVis also enables automated nucleus and cytoplasmic segmentation from H&E images, facilitating extraction of nuclear-cytoplasmic localization.

We also perform VisiumHD of mouse liver sections and identify mRNAs that are polarized towards the sinusoidal facing basal cell compartment.

HiVis facilitates both tissue-level zonation reconstruction, and automated or guided detection of sub-cellular compartments to extract intra-cellular mRNA localization patterns. We demonstrate this by resolving apical-basal mRNA polarization in mouse intestinal epithelium.

Intracellular mRNA polarization is hard to study in intact tissues. We developed HiVis: pypi.org/project/HiVis/, a computational Python package that combines image processing with transcriptomics to extract these features from VisiumHD datasets.

Happy to share our new preprint: Subcellular mRNA localization patterns across tissues resolved with spatial transcriptomics: www.biorxiv.org/content/10.1...
We utilize VisiumHD to extract intra-cellular mRNA polarization patterns in epithelial tissues.

EPB41L4A-AS1 long noncoding RNA acts in both cis- and trans-acting transcriptional regulation and controls nucleolar biology Mammalian genomes are pervasively transcribed into long noncoding RNAs (lncRNAs), whose functions and modes of action remain poorly understood. EPB41L4A-AS1 is an evolutionary conserved, broadly and h...

New preprint 📜 from @AlanMonziani in the lab – EPB41L4A-AS1 long noncoding RNA acts in both cis- and trans-acting transcriptional regulation and controls nucleolar biology www.biorxiv.org/content/10.1... . A🧵

Hadas Keren-Shaul, Liat Fellus-Alyagor, Dana Hirsch, Chen Mayer, Ron Pery, Niv Pencovich, Timucin Taner, Ido Nachmany, Weizmann Institute, Sheba Medical Center, Mayo Clinic.

7/ Huge shoutout to the amazing team behind this:
Oran Yakubovsky, Amichay Afriat, Adi Egozi, Keren Bahar Halpern, Tal Barkai, Yotam Harnik, Yael Korem Kohanim, Roy Novoselsky, Ofra Golani, Inna Goliand, Yoseph Addadi, Merav Kedmi,

6/ Our data, including Loupe files for Visium & VisiumHD, is open access for exploration:
Zenodo: zenodo.org/records/1479...
Web browser: itzkovitzwebapps.weizmann.ac.il/webapps/home...

5/ We also developed AI-based lipid classification for Visium spots, revealing dynamic expression changes in early steatosis: First, early steatotic hepatocytes build lipids (↑ FASN, MLXIPL). Then, they shift to increased insulin & adiponectin receptor expression.

4/ Key hepatic functions show pericentral shifts in humans, including: Mitochondrial gluconeogenesis (PCK2), Urea cycle (NAGS, OTC), Respiration genes and the Key TF HNF4A.

3/ Most human hepatocyte genes are zonated, but zonation patterns in humans differ dramatically from those in mice and even large mammals (cow, pig, boar) which we also profiled.

2/ Using Visium, VisiumHD, and MERFISH on 16 patients, we uncovered striking differences between live donor liver and the commonly used 'adjacent normal' liver samples. Live donor liver shows lower immune gene expression and higher hepatocyte program expression.

1/ The liver's remarkable regenerative capacity allowed us to study gene expression programs in live healthy donors (LHDs) - a unique opportunity to understand human liver biology.

Happy to share our new preprint: A spatial transcriptomics atlas of live donors reveals unique zonation patterns in the healthy human liver: www.biorxiv.org/content/10.1...

Intracellular polarization of RNAs and proteins in the human small intestinal epithelium The intestinal epithelium is a polarized monolayer of cells and both proteins and mRNAs have been shown to have global basal-apical polarization in mice. These authors perform a systematic analysis of...

What a cool new story by @shalevitzkovitz.bsky.social! They show which proteins and RNAs are expressed in the apical vs basal sides of intestinal epithelial cells (mice and humans). Some really interesting phenomenons
@plosbiology.bsky.social @npariente.bsky.social
journals.plos.org/plosbiology/...