Omer Ali Bayraktar
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bayraktarlab.bsky.social
Omer Ali Bayraktar
@bayraktarlab.bsky.social
Group leader
@sangerinstitute.bsky.social Neural diversity, spatial transcriptomics, glia, GBM
We implicated thalamic excitatory neurons in particular, and many of the thalamus expressed genes are involved in neuronal & synaptic function
November 11, 2025 at 10:55 AM
While we expected the developing human cortex to be the most “important” region, we found the most prevalent expression of autism susceptibility genes in the developing human thalamus!
November 11, 2025 at 10:55 AM
Here, we mapped the expression of 250 known autism susceptibility genes in >10 million cells across the developing human forebrain using Xenium spatial transcriptomics
November 11, 2025 at 10:55 AM
Which human brain circuits are implicated in neurodevelopmental conditions? We bridged human genetics, spatial transcriptomics and neurodevelopment to discover the convergence of autism-associated genes in the developing human thalamus! www.biorxiv.org/content/10.1...
November 11, 2025 at 10:55 AM
Taken together, these 2 studies start to unveil what i call the “rules” of glioblastoma. Despite their incredible complexity, these tumours are governed by specific cellular & tissue mechanisms. We believe/hope this understanding will be a foundation for new therapies
May 16, 2025 at 11:44 AM
In GB, as opposed to unrestrained plasticity of cancer cells, we predict transition highways and barriers aligned with paper 1. And we mechanistically validate a transcriptional repressor safeguarding neuronal like cancer states!
May 16, 2025 at 11:44 AM
scDORI enables us to examine GRNs in a continuous manner across cellular trajectories. Hence, you don’t just map GRNs / TF regulators, you can actually infer cell plasticity and predict the future state of a given cell
May 16, 2025 at 11:44 AM
In paper 2, we leverage our massive snRNA-ATACseq data to predict cancer cell state transitions & trajectories from gene regulatory networks. Led in @oliverstegle.bsky.social and Moritz Mall's labs by @manusaraswat.bsky.social @lauraruedag.bsky.social Elisa + Tannia & Fani
May 16, 2025 at 11:44 AM
Hence, we define a stereotyped trajectory of cancer cells at the heart of GB heterogeneity - unifying previously defined cell states & tumour subtypes
May 16, 2025 at 11:44 AM
Finally, cancer cells are not riding alone. We found that this cancer cell trajectory is intimately linked to myeloid heterogeneity and unfolds across regionalised myeloid signalling environments.
May 16, 2025 at 11:44 AM
This led to a wonderful side quest: we mapped tumour subclones in space! We developed SpaceTree to deconvolve tumour subclones in Visium data and found that they are finely spatially intermixed (within Visium spots) in the tissue! github.com/PMBio/spaceT...
May 16, 2025 at 11:44 AM
These results suggest that this trajectory cuts across the genetic hierarchy of GB i.e. shared across tumours/subclones. We used spatial DNA-seq (LCM-WGS) to validate this +found the trajectory is shared, yet genetically malleable.
May 16, 2025 at 11:44 AM
Unbiased transcriptomic trajectory analysis (i.e. our cell2fate RNA velocity go.nature.com/4km62aI) finds that this is trajectory shared across tumours + genetic subclones. And we define a molecular progression conserved across tumours/clones
May 16, 2025 at 11:44 AM
When you look into the tumour areas/states dominated by gliosis/hypoxia, these transitions become clear. You can see cancer cells travelling from developmental astrocyte like states gradually into gliosis + hypoxia response (more on this below)
May 16, 2025 at 11:44 AM
..to resolving this trajectory. Integrating single nuclei + spatial data revealed stepwise spatial transitions of cancer cell states from the tumour invasive edge towards the necrotic core. This looked like spatially organised cancer cell transitions as GB tumours rapidly expand.
May 16, 2025 at 11:44 AM
It started with single nuclei RNA-seq. Profiling >1 million cells, we saw within each tumour that cancer cells vary from developmental progenitor-like states (e.g.NPC/OPC) to those marked by gliosis (i.e. glial injury response) & hypoxia Yet, the spatial/tissue context was the key…
May 16, 2025 at 11:44 AM
Integrating these modalities, we interpreted human GB biology from scratch. We mapped GB heterogeneity to a spatially-patterned trajectory of cancer cells in tissue, where they transition from developmental-like towards glial injury response & hypoxia states.
May 16, 2025 at 11:44 AM
In paper 1, we tackled this big question. We created the GBM-space, the most comprehensive atlas of human GB. It uniquely pairs single cell + spatial modalities to bridge the cell, tissue and genetic basis of GB. Led by the amazing team of Grant, Tannia, Fani & Olga
May 16, 2025 at 11:44 AM
Glioblastoma (GB) is a rapidly fatal brain tumour. Within each GB tumour, cancer cells exist across diverse cellular states + can switch their states (i.e. plasticity) + are thought to make tumour subtypes….
May 16, 2025 at 11:44 AM
Over the past 3 years, we led a fantastic @wellcomeleap.bsky.social collaboration w. @oliverstegle.bsky.social, Behjati, Mall, Mair, @jamesbriscoe.bsky.social & @juliosaezrod.bsky.social labs. We created a massive multiomic atlas & new comp models to discover human GB biology www.gbmspace.org
May 16, 2025 at 11:44 AM
How does tumour heterogeneity arise? How can we predict cancer cell plasticity? In 2 new studies, we trace #glioblastoma heterogeneity to a spatial cancer cell trajectory w. multimodal cell atlassing bit.ly/4mkrWgs & predict plasticity w. snRNA/ATAC+deep learning bit.ly/3FbI6Ic 🧵
May 16, 2025 at 11:44 AM