Louise Huuki-Myers

And of course thanks to @lcolladotor.bsky.social @kr-maynard.bsky.social @martinowk.bsky.social

two men sitting next to each other with the words " teamwork makes the dream work " on the bottom ALT: two men sitting next to each other with the words " teamwork makes the dream work " on the bottom

Thank you to all of our collaborators at the @lieberinstitute.bsky.social for their excellent work on this project! 🧑‍🔬 @heenadivecha.bsky.social @svitlanabach.bsky.social @madelinevalentine.bsky.social @nick-eagles.bsky.social @berniejmulvey.bsky.social and UK collaborators @jamesrevans.bsky.social

This dataset is paired with a spatial transcriptomic analysis of the locus coeruleus from the same donors. This work led by @berniejmulvey.bsky.social is also now in pre-print!
bsky.app/profile/berniejmulvey.bsky.social/post/3m4isvuqabm2v
www.biorxiv.org/content/10.1...

Many exciting findings here inspire future work! Next we'll explore Oligo.3 to see if this signal is present in AD donors and check how upstream events in the circuit connecting the locus coeruleus and the ERC may drive disease. Keep an eye on @lieberinstitute.bsky.social for more AD research! 🧠

Screenshot from spatial LIBD web-app for exploring ERC SRT data

This ERC SRT and snRNA-seq data is available to explore via our interactive websites research.libd.org/LFF_spatial_ERC/ and available for download via #spatialLIBD 💻 🔓 #opendata

barplot of number of ancestry-specific DEGs. Venn diagram of overlap between African and European ancestry DEGs in Oligo.3. Scatter plot of DE t-statistics from each ancestry group.

The risk effect of #APOE is ancestry dependent, and the diverse set of donors in our study allowed us to assess this in our data. Oligo.3 was the major source of DEGs in both African and European ancestry, but DEGs were quite different between the two ancestries

Proposed model for oligodendrocyte subcluster classification and maturation trajectory in APOE E2+ and E4+ carriers

This pattern of downregulation of #oligodendrocyte maturation genes in pre-mylenating Oligo.3’s led us to hypothesize that the maturation of oligos is reduced in the #APOE E4+ ERC, which could lead to reduced myelination, rendering neurons more vulnerable to degradation in #Alzheimers disease

Volcano plot of Oligo.3, boxplots of select DEGs, heatmap of top up and downregulated DEGs in Oligo subtypes, top DEG enriched GO terms from Oligo.3

Examining the gene expression changes in Oligo.3 between #APOE carriers, genes up-regulated in E4+ were enriched in synaptic signaling & metal ion transport, down-regulated genes enriched in myelination & #oligodendrocyte development

tSNE plot of OPC and Oligo subclusters with trajectory analysis, Centered and scaled log-normalized gene expression of Oligo subcluster marker genes, cartoon of subclusters along oligo maturation process.

The strong AD risk signal in this #oligodendrocyte subtype prompted a closer look at the identity of Oligo.3. Marker genes and a trajectory analysis suggest Oligo.3 is a pre-myelinating oligodendrocyte, perhaps the earliest stage of oligos differentiating from OPCs

Design of differential expression analysis in clusters between APOE E4+ and E2+ donors. Bar plot of number of DEGs from each cluster in SRT and snRNA-seq data, subcluster Oligo.3 had the majority of DEGs.

To explore gene expression changes in AD risk, we performed differential expression analysis with #voomLmFit on ERC clusters between high risk #APOE E4+ and low risk E2+. We found a large number of differential expressed genes in an oligodendrocyte subcluster Oligo.3 #edgeR #limma

TSNE plot and hierarchical clustering of cell types in snRNA-seq data from human ERC

In addition we generated the largest public ERC #snRNAseq dataset, 122k nuclei clustered into 38 fine resolution sub-clusters. Taking a close look at the cellular diversity of the brain region 🔍 🦠

Three representative SRT ERC samples, showing histology, expression of marker genes MBP, PCP4, and SNAP25, and spatial domains

We used #Visium to generate the FIRST spatial transcriptomics dataset of the human #entorhinal cortex. By profiling gene expression across ERC layers with #BayesSpace and #spatialLIBD we uncovered gene expression patterns that could be useful in #Alzheimers research 🧠

Experimental design for LIBD LFF Spatial ERC project

Excited to share our latest preprint from @lieberinstitute.bsky.social spatial + single-cell RNA-seq map the ERC & explore how AD risk shapes gene expression doi.org/10.1101/2025...
Our major finding: “APOE E4 Alzheimer’s Risk Converges on an Oligodendrocyte Subtype in the Human Entorhinal Cortex”

Inside the Habenula: Lieber Institute Researchers Uncover a Hidden Player in Schizophrenia About the size of a pea, the habenula serves as a hub connecting key brain systems that regulate motivation, mood, and reward — all of which are disrupted in schizophrenia. Yet until now, the habenula...

For more, check the @lieberinstitute.bsky.social announcements at
🔗 www.libd.org/tiny-brain-r...
🔗 www.libd.org/inside-the-h...
As well as the American Psychiatry Association press release
🔗 www.psychiatry.org/News-room/Ne...

Unlocking the Molecular Secrets of the Human Habenula | American Journal of Psychiatry PsychiatryOnline.org is the platform for all American Psychiatric Association Publishing journals, DSM, and bestselling textbooks, as well as APA Practice Guidelines, and continuing medical education.

Thanks to @nataliematosin.bsky.social and Sophie Debs for highlighting our work in their editorial “Unlocking the Molecular Secrets of the Human Habenula”
🔗 doi.org/10.1176/appi...

This data provides a foundation for future work into molecular changes that occur in the #Habenula in disease 🧠🧬 Keep an eye on @lieberinstitute.bsky.social for future work on the Hb spatially resolved transcriptomics with @10xgenomics.bsky.social tech #Visium and #Xenium 👀 #HabenulaLIBD

GitHub - LieberInstitute/Habenula_Pilot: habenulaPilot project code repository habenulaPilot project code repository. Contribute to LieberInstitute/Habenula_Pilot development by creating an account on GitHub.

Our #Habenula #singlecell and differential expression data is available to explore via our interactive websites 💻 #opendata github.com/LieberInstit...

We used #eQTL analysis to examine how SNPs relate to gene expression in #Habenula, 7 eQTLS genes were identified in differential expression, and 16 eSNPs were schizophrenia GWAS risk SNPs. Nine new schizophrenia colocalized genes with genetic risk were identified

We investigated whether the DEGs we found were unique to the #Habenula vs. other brain regions studied in schizophrenia (Caudate, Dentate Gyrus, dlPFC, Hippocampus) and found 75% of our DEGs were unique to habenula 🦄

Differential gene expression yielded 173 differentially expressed genes between schizophrenia and control donors, some of which support the neurodevelopmental hypothesis of schizophrenia 🌋

To refine habenula signal from neighboring thalamus we utilized our #snRNAseq data to perform #deconvolution on our bulk samples, estimating proportion of habenula. These proportions were used to control for dissection differences in the differential expression analysis

We also profiled habenula-enriched tissue from schizophrenia and control donors using bulk RNA-seq #Transcriptomics, generating a unique dataset to identify disease associated molecular changes. PCA with bulk data from other regions shows #Habenula as an outlier

To provide cross-species context we integrated our human Hb snRNA-seq dataset with a previously published mouse #Habenula #singlecell dataset from @gstuber.bsky.social. Some neuronal subclusters such as human OPRM1-enriched LHb.2 appeared to be conserved across species 🐁

Single molecule fluorescence in situ hybridization #RNAScope and HALO from @indicalabs.bsky.social was used to visualize the spatial organization of these human Hb neuronal populations. 🔬 For example, MHb.2 neurons that highly expressed CHAT clustered separately from other MHb cell types

We’ve created a #snRNAseq molecular atlas of the human Habenula to understand neuronal diversity on a molecular level in this unique brain region. Our snRNA-seq data on 7 control donors yielded 16k nuclei and 17 clusters, including 7 lateral & 3 medial Hb neuron populations 🧪

Thank you to all of our collaborators at the @lieberinstitute.bsky.social for their dedication and hard work on this project! 🧑‍🔬 #HabenulaLIBD @freneegf.bsky.social @nick-eagles.bsky.social @lcolladotor.bsky.social @kr-maynard.bsky.social @martinowk.bsky.social

Transcriptomic Analysis of the Human Habenula in Schizophrenia | American Journal of Psychiatry Objective: The objective of this study was to define the molecular neuroanatomy of the human habenula (Hb) and identify transcriptomic differences between brains of individuals with schizophrenia and ...

Proud to announce our paper ‘Transcriptomic Analysis of the Human Habenula in Schizophrenia’ from @lieberinstitute.bsky.social is the cover article for the November issue of the American Journal of Psychiatry! 🧠 #HabenulaLIBD #snRNAseq #Habenula doi.org/10.1176/appi...

Learning more about APOE differences in the cell types of the brain 🧠

I presented "APOE genotype determines cell-type-specific pathological landscape of Alzheimer’s disease" from @zhaonaa.bsky.social at our team journal club, check it out!

doi.org/10.1016/j.ne...

▶️ youtu.be/L4J9jFS-Pic

[2025-04-23] Journal club on "[...] deconvolution of pooled snRNA-seq using sex-dependent gene expr" YouTube video by Leonardo Collado Torres

Hi! Check my journal club talk: smart ML method to deconvolute pooled snRNA-seq using sex-specific expression🧬

Thanks @daylab.bsky.social & @rphillips3.bsky.social for this approach🙌

🎥 youtu.be/zpeCFwYfV3o
🛝 speakerdeck.com/manishabarse

#snRNAseq #ML #Bioinformatics @lieberinstitute.bsky.social