The webinar series on spatial transcriptomics analysis is now open for registration!
Join me on 18 March to learn how we at @bayraktarlab.bsky.social integrate single-cell and spatial transcriptomics to map the rules of neurological conditions.
Grateful to @hilarycmartin.bsky.social, Tom Nowakowski and all the other authors and @simonsfoundation.org for the funding
3) Our work suggests thalamocortical circuit development is a major hub of autism susceptibility & organoid/animal models of autism need to take this into account
2) Hyper/hypo sensitivity are amongst core autism symptoms and sensory sensitivities can be highly distressing & impair social communication.
Why is this important:
1) Thalamus is a brain region essential for sensory processing and social cognition. It is deeply & reciprocally connected with the cortex, where information from your senses is relayed to the cortex through the thalamus.
After the thalamus, the germinal zones that house neural progenitors are most heavily implicated, especially interneuron progenitors! See the preprint for more!
We implicated thalamic excitatory neurons in particular, and many of the thalamus expressed genes are involved in neuronal & synaptic function
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!
Here, we mapped the expression of 250 known autism susceptibility genes in >10 million cells across the developing human forebrain using Xenium spatial transcriptomics
by looking them up in single cell transcriptomic atlases of the developing human brain. However, neuroscience is very “cortex-centric” - it is the most accessible & widely studied brain region - neuroimaging & behavioural symptoms implicate other brain areas.
When & where are these genes expressed during human brain development? These are key questions towards understanding the biology of profound autism. Previous work suggested that autism susceptibility genes converged in the developing human cerebral cortex...
Autism is also highly heritable. In >10% of autistic individuals, rare & de novo coding genetic variants (i.e. leading to loss of protein function) predispose individuals to profound autism. We know of >200 “autism susceptibility genes” with such variants.
First & foremost, autism exists across a wide spectrum. Our work is focused on profound autism that co-occurs with developmental and intellectual disability (e.g. non-verbal / minimal communication).
Work by the awesome team of Alexander, Fani and @krademaker.bsky.social
Explore the data interactively (>10 million cells spatially mapped across the developing human brain): www.stageatlas.org
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...
NEW: Technical specialist with @bayraktarlab.bsky.social
Generate large-scale spatial transcriptomic datasets to create comparative cell atlases of ALS, Alzheimer’s disease and Parkinson’s disease
#scienceJobs #neuroskyence
sanger.wd103.myworkdayjobs.com/en-US/Wellco...
NEW: Postdoc in neurodegenerative disease spatial transcriptomics and ML with @bayraktarlab.bsky.social/Mo Lotfollahi
Join a new project to create comparative cell atlases of ALS, Alzheimer’s disease and Parkinson’s disease
#postdocJobs #neuroskyence
sanger.wd103.myworkdayjobs.com/en-US/Wellco...
📢 @bayraktarlab.bsky.social & colabs at @sangerinstitute.bsky.social are assembling the @opentargets.org funded Neuroimmune Team 🧠🧬-Leverage AI to uncover neurodegeneration
Tech Spec: sanger.wd103.myworkdayjobs.com/en-US/Wellco...
Postdoc AI: sanger.wd103.myworkdayjobs.com/en-US/Wellco...
Very excited about our new chapter with @mhaniffa.bsky.social !
Thanks Muzz!
Thanks Adrien!
Two massive glioblastoma papers, datasets, trajectories, insights, and.. a very cool new method for GRN inference - scDORI -from @steglelab.bsky.social @oliverstegle.bsky.social @bayraktarlab.bsky.social & Moritz Mall www.biorxiv.org/content/10.1... www.biorxiv.org/content/10.1...
Thanks Chris!
Grateful to >60 authors for their amazing work + @wellcomeleap.bsky.social (special thx to Jason Swedlow for leading DeltaT!) & @cziscience.bsky.social for their support. @ebi.embl.org @crick.ac.uk @cambridgeuni.bsky.social @dkfz.bsky.social @sangerinstitute.bsky.social
Finally, you can access & navigate almost all of our GB single cell and spatial data in our portal @ www.gbmspace.org built with webatlas2 (go.nature.com/4dEr9mN)
There are many implications & LOTS of detail in the preprints (e.g. mesenchymal cancer states is really a gliosis/hypoxia response & GB tumour subtypes are likely confounded) bit.ly/4mkrWgs bit.ly/3FbI6Ic
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
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!
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
Here we developed a new deep learning based GRN inference framework: scDORI. See the thread from Manu for more details but few highlights here bsky.app/profile/manu...
