Thrilled to present our comparative study on the evolution of zygotic genome activation (ZGA)!! 🥚🧬
Amazing PhD work of @campobes.bsky.social together with @fedemantica.bsky.social and many collaborators! @melisupf.bsky.social @crg.eu. Thread below 1/15
www.biorxiv.org/content/10.6...
Evolutionary landscapes of zygotic genome activation across animals www.biorxiv.org/content/10.64898/2026.04...
Whole organism 3D mapping reveals universal branching topology and biophysical optimization governs vascular and nervous system development
Read about our work here: www.biorxiv.org/content/10.6...
New manuscript with Rory Cerbus and Ichiro Hiratani. We analyzed 3D genome data from 247 species to investigate the determinants of the so-called large-scale structure known as compartments. www.biorxiv.org/content/10.6...
New preprint @cxqiu.bsky.social @jshendure.bsky.social ! Can we learn regulatory grammars of human cell types — by training on mouse development and transferring across 241 mammalian genomes? Introducing STEAM & a whole-organism scATAC-seq atlas from E10 to birth.
www.biorxiv.org/content/10.6...
Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes www.biorxiv.org/content/10.64898/2026.04...
New preprint from the lab!
How do tissue shapes influence cell fate decisions?
By manipulating brain organoid geometry, we show that lumen rounding directs apical progenitor division mode and promotes the emergence of basal progenitors.
www.biorxiv.org/content/10.6...
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Why do schizophrenia GWAS signals look so flat across the genome?
In our recent preprint, we explored why psychiatric disorders — and, more broadly, brain-related traits involving the central nervous system — appear to have unusual genetic architectures.
🧵1/n
graphical abstract for "Developmental determinants of male bias in medulloblastoma" preprint. We propose that boys are more likely to develop Group 3/4 medulloblastoma more vulnerable cells-of-origin are available for transformation. Specifically, GC_UBC progenitors in the developing cerebellum are more abundant in male murine embryos, as a result of testosterone exposure and the XY genotype.
New preprint alert! I'm excited to share our latest preprint where we investigate the underlying developmental causes of the male bias in the pediatric brain tumor Group 3/4 medulloblastoma. www.biorxiv.org/content/10.6...
We built the first complete genome for the common marmoset, fully resolving regions that were previously missing: centromeres, acrocentric short arms, and more. A new reference genome for anyone working with marmosets. This was an awesome collaborative effort & I’m grateful to all my co-authors! 🧬
We wrote a review on using machine learning to study evolutionary genetics and molecular evolution in Trends in Genetics. It is open access—please take a look if you are interested in this topic www.sciencedirect.com/science/arti... @cp-trendsgenetics.bsky.social
Modeling cis-regulatory variation in human brain enhancers across a large Parkinson's Disease cohort www.biorxiv.org/content/10.64898/2026.03...
ChromSMF preprint is out!🚀
tinyurl.com/ChromSMF
We often piece together chromatin regulation layer by layer from separate assays. But this can be limiting!
In @arnaudkr.bsky.social's lab, we developed a method to directly study multiple layers on the same DNA molecule! 🧬
What does this unlock? ⬇️
MPRAs are the gold-standard tool for measuring how DNA sequences drive gene expression and prioritizing variant effects.
In this preprint we asked: does it matter WHERE you place a variant in an MPRA?
Spoiler: yes, and it might lead you to miss disease-causing variants. 1/6
doi.org/10.64898/202...
Excited to share that our work is now published in Cell: Human-specific features of the cerebellum and ZP2-regulated synapse development. www.cell.com/cell/fulltex...
Many thanks to the Sestan lab members @yaleneuro.bsky.social and all collaborators who made this work possible.
Inhibitory neurons are among the most transcriptomically diverse class of neurons in the CNS, with some brain regions having 60+ distinct cell types. Do humans share the same repertoire as rodents? Birds? Fish? 1/13
New Perspective form Rory Maizels & me: "Gene regulatory networks: from correlative models to causal explanations"
Gene regulatory networks are supposed to give us mechanistic explanations of development, so why are we drowning in 'hairballs' of statistical correlations?
rdcu.be/e7zx7
Figure 1.(A) Classical gel electrophoresis experiments showing mono-, di-, tri-, tetra-, and further multinucleosome bands upon chromatin digestion. (B) The nucleosome repeat length (NRL) is defined as the genomic distance between the centres of two neighbouring nucleosomes.
Figure 2.Nucleosome mapping using MNase-seq versus ATAC-seq. (A) In MNase-seq, nucleosomes in both open and tightly packed genomic regions are accessible to digestion. MNase preferentially cleaves DNA between nucleosomes and digests DNA until it encounters a histone octamer, which provides a footprint of nucleosome-protected DNA regions. (B) Bulk MNase-seq results in averaged maps across millions of cells, effectively capturing all possible nucleosome positioning configurations. (C) Single-cell MNase-seq (scMNase-seq) results in a noisier and sparser signal. The resulting footprints still represent nucleosome-protected regions, but not all nucleosomes are represented. (D) In ATAC-seq, open regions can be accessed by the enzyme Tn5 transposase, which can insert primers in regions free from the binding of nucleosomes and transcription factors (TFs). (E) For open chromatin regions, nucleosome maps can be obtained from ATAC-seq similar to MNase-seq. (F) Closed, tightly packed chromatin regions may be less represented in ATAC-seq nucleosome maps.
Figure 5.Molecular mechanisms affecting nucleosome spacing. (A) Linker histones H1 and nonhistone chromatin proteins which compete with H1s and modulate nucleosome spacing through structural and electrostatic mechanisms. (B) Chromatin remodellers actively reposition nucleosomes following context-dependent rules. (C) Cell state-dependent chromatin boundaries formed by CTCF and other structural proteins, as well as associated recruitment of chromatin remodellers which space nucleosomes. (D) Gene activity associated with remodeller action and RNA polymerases transcribing through the nucleosomes, leading to smaller distances between nucleosomes in regulatory regions and gene bodies. (E) DNA sequence repeats of different types.
![Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:7rjg5hcnnloxgwuvwi23aixu/bafkreihl7mkdtxojw23qoqxm7yt57frzc24mjjllszhbohbvb67ffguccy)
Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).
Nucleosome aficionados! Our new review "Nucleosome spacing across cell types, diseases, and ages" is out in NAR: academic.oup.com/nar/article/...
A huge effort to pull together what we’ve learned about nucleosome spacing in many systems. Enjoy!
@milena-bikova.bsky.social @chrsclrksn.bsky.social
Find our latest Perspective article in Nature Genetics on "The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements" at www.nature.com/articles/s41..., with implications for the future of research on the cause of human disease.
Happy to share that our work with Ekaterina Osipova, @maggiemcko.bsky.social, Tim Sackton, Maude Baldwin & fantastic collaborators on convergent and lineage-specific genomic adaptations in sugar-feeding birds is published in Science www.science.org/doi/10.1126/.... While high sugar intake ...
Our most recent work on the “function and evolution” of #nuclear-speckles is now online at Cell @cp-cell.bsky.social
doi.org/10.1016/j.ce...
Read the thread👇 for the highlights of our findings.
Our internal organs are evolutionary marvels. New technologies are transforming our understanding of the evolution of vertebrate organs. You can find more by reading here:
rdcu.be/e5EgU
#EvoBio #EvoDevo 🐟🦎🐢🦇🐊🦜
Have you ever wondered 🤔... Does phenotypic variance respond to environmental perturbation? Does it have a genetic basis? Are mean and variance regulating loci exposed to different selection pressures? These and more questions are explored in our new preprint 🔥
www.biorxiv.org/content/10.6...
From our new paper out now in @currentbiology.bsky.social: www.cell.com/current-biol... w/ @neurofishh.bsky.social @gkafetzis.bsky.social @denilsson.bsky.social
Looking across animals, the vertebrate eye is an obvious outlier. Why is it so different that other highly visual animals?
Interested in the evo-devo of the mammalian cerebellum? This review is a must-read!
Really happy to have contributed to this work, led by @marisepp.bsky.social , together with @ioansarr.bsky.social .
Brain with puzzle overlay to show that our study provides missing pieces of the puzzle of human brain development by delivering the most comprehensive picture of hindbrain development to date. We have strived to go beyond just another multi-omics atlas to gain deep insights by: 1. Meticulously annotating cell clusters 2. Extracting regulatory programs in terms of coordinated gene sets and accessible regulatory elements 3. Using deep learning to identify regulatory syntax 4. Resolving context-specific TF activity
Excited to share our preprint on our new multi-omic atlas of human hindbrain development. Led by postdoc Piyush Joshi, in collaboration with @kaessmannlab.bsky.social and Pfister labs, our atlas represents the first comprehensive view of human hindbrain development. www.biorxiv.org/content/10.6...
Exciting Postdoc Opportunities – Alliance Interinstitutional Program
**Deadline:** March 31, 2026 (5:00 pm CEST)
🔗 Two shared positions: www.syn-gen.de/alliance-pos...
🔗 Full call & application info:: www.health-life-sciences.de/opportunitie...
Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure.
We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)
The new updates for Charles McAnany’s preprint “Positional Interpretation of Cis-Regulatory Code and Nucleosome Organization with Deep Learning Models” (www.biorxiv.org/content/10.1...) are up!
We introduce PISA, a tool to visualize the cis-regulatory code. See a recap below:
