Boyan Bonev

Boyan Bonev

@boyanbonev.bsky.social

Group Leader at Helmholtz Center Munich * Brain Epigenomics

410 followers198 following25 posts

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Can a stem cell change its epigenome while proliferating? In collaboration with the lab of Amos Tanay, we demonstrate that yes, the epigenome of neural stem cells (NSCs) is continuously remodeled, across multiple layers, during mouse corticogenesis. 1/14 www.biorxiv.org/content/10.1...

biorxiv.orgNeural stem cell epigenomes and fate bias are temporally coordinated during corticogenesisThe cerebral cortex orchestrates complex cognitive functions, yet how its distinct temporal lineages are molecularly patterned during development remains unresolved. Here, we integrate single-cell tra...

Boyan Bonev reposted

🚀 𝗣𝗼𝘀𝘁𝗱𝗼𝗰 𝗢𝗽𝗲𝗻𝗶𝗻𝗴 We’re recruiting an ERC-funded Postdoctoral Researcher to explore how 3D gene regulatory networks evolved during human and primate brain development, using cutting-edge single-cell multiomics, organoid models, and CRISPR screens. 👉 Apply by Nov 30 | www.bonevlab.com/join

Boyan Bonev reposted

Boyan Bonev reposted

Boyan Bonev reposted

Boyan Bonev reposted

Are you @ the late stages of your postdoc ? Want to pursue a PI career ? Then this 👇👇 is for you ! Apply for a spot @ our Talent Forum www.helmholtz-munich.de/en/stem-cell... Peer-networking / Career orientation and more !!! Please distribute :) 🙂

🎤 Postdocs: want to take the next step and become a #PI? Apply to speak at the TALENT FORUM @www.helmholtz-munich.de, showcase your research in Epigenetics & Nucleic Acids, and connect with top scientists. 🧳 Travel & accommodation covered if selected! 📝 Apply by 31July. 🔗 Info: lnkd.in/drkRvz7N

Boyan Bonev reposted

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis 🧬🩸 screen of fully synthetic enhancers in blood progenitors 🤖 AI that creates new cell state specific enhancers 🔍 negative synergies between TFs lead to specificity! www.cell.com/cell/fulltex... 🧵

cell.comDesign principles of cell-state-specific enhancers in hematopoiesisScreen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

Boyan Bonev reposted

We also show explicitly that NSC methylation has a repressive effect on IPC accessibility, and that cooperativity between proximal CREs is correlated with accessibility both in terms of sequence content and total proximal activation. 11/14

Finally, we assayed the activity of thousands of CREs isolated from their genomic context across multiple timepoints in vivo using a cell-type-specific massively parallel reporter assay. We showed that cell type-specificity is encoded in the sequence, in agreement with our quantitative model. 12/14

We developed a machine-learning model that integrates sequence (putative TF motifs, dinucleotide content) and epigenomic features (ATAC, methylation, proximal activity) to predict NSC<->IPC specificity of CREs, that yields R^2 = 0.62 on held-out data. 10/14

Temporally activating CREs are significant: they are enriched with astrocyte-specific CREs, and astro CREs undergo extensive demethylation within NSCs across time, in contrast to other cell type-specific CREs. 7/14

Our Hi-C analysis shows that while overall chromatin topology is conserved across time in NSCs, there are specific hotspots whose differential insulation across time is correlated with the presence or depletion of proximal CREs. 8/14

Furthermore, we were able to identify CREs with dynamic accessibility within cell types, across time. We focused on CREs that either activate/increase accessibility, or deactivate over time in NSCs. 5/14

We found that ATAC-activating CREs are tightly concomitant with methylation decrease. But the opposite was not true! Deactivating CREs in NSCs stay unmethylated across our time series, and this is not due to absence of DNMTs. 6/14

We show that astrocyte genes in NSCs are upregulated gradually over time, not suddenly, along with erosion of NSC proliferative capacity. This erosion is also correlated with lengthening of the cell cycle, suggesting that NSC fate bias is coupled to the cell cycle. 3/14

Our metacell model of ATAC states provides a high-resolution timeline of cis-regulatory element (CRE) accessibility in corticogenesis. We use it to show that CREs specific to corticofugal neurons are activated late in maturation, in stark contrast to callosal projection neuron-specific CREs. 4/14

Can a stem cell change its epigenome while proliferating? In collaboration with the lab of Amos Tanay, we demonstrate that yes, the epigenome of neural stem cells (NSCs) is continuously remodeled, across multiple layers, during mouse corticogenesis. 1/14 www.biorxiv.org/content/10.1...

biorxiv.orgNeural stem cell epigenomes and fate bias are temporally coordinated during corticogenesisThe cerebral cortex orchestrates complex cognitive functions, yet how its distinct temporal lineages are molecularly patterned during development remains unresolved. Here, we integrate single-cell tra...

We have generated one of the most comprehensive multiome datasets in the context of brain development, integrating time-series measurements of scRNA-seq, scATAC-seq, 5mC methylation and Hi-C of mouse somatosensory cortex across 6 developmental timepoints. 2/14

Overall, we systematically link 3D epigenome evolution to gene expression changes in the context of primate brain development. This integrative approach significantly advances our understanding of how divergent regulatory networks and epigenome dynamics contribute to human brain evolution

High-resolution Hi-C revealed unexpected global shifts in 3D genome architecture in the chimpanzee and gorilla NSC, while topologically associating domains remained remarkably conserved. #3DGenome #HiC

Species-specific genes were often associated with multiple differentially accessible regions, suggesting that synergistic enhancer activation is a key mechanism driving epigenome evolution. #EnhancerSynergy #GeneRegulation

We also proposed the emergence of novel TF motifs and specific class of transposable elements - SVA, as one of the key drivers of species- and cell type-specific chromatin accessibility — linking DNA sequence to epigenome evolution.

We have generated one of the most comprehensive datasets of primate epigenome evolution to date — profiling and integrating genome-wide 3D genome organization, chromatin accessibility and gene expression in human, chimpanzee, gorilla and macaque IPSC and neural stem cells (NSC).

We identified novel human-biased genes and epigenetic signatures and further validated them using cortical organoids and MPRA data to generate a set of highly confident putative enhancers - paving the way for future functional studies of human brain development. #ComparativeGenomics

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