We are thrilled that our study on the evolution of gene regulation in mammalian cerebellum development – led by @ioansarr.bsky.social, @marisepp.bsky.social and @tyamadat.bsky.social, in collaboration with @steinaerts.bsky.social – is now out in @ScienceMagazine! www.science.org/doi/10.1126/...
Exciting news to start the new year! We’re thrilled to see this work finally out in @natecoevo.nature.com, the result of a major collaboration between my lab and the labs of Veronica Hinman and Nacho Maeso, began many years ago with the dear José Luis Gómez-Skarmeta.
www.nature.com/articles/s41...
Excited to share the final version of our study on Nematostella cell type regulatory programs. Part of our @erc.europa.eu StG project, this was a challenging 5-year effort extraodinarily led by @aelek.bsky.social and @martaig.bsky.social.
www.nature.com/articles/s41...
Lovely Xmas gift 🎄—our paper is out today in @natecoevo.nature.com www.nature.com/articles/s41...! Huge thanks to everyone who made it possible, especially @aelek.bsky.social and @arnausebe.bsky.social
Science: only when you write up the manuscript, you realize what you should have done.
We are happy to share our latest work in @nature.com . We study the genomic and cellular basis of facultative symbiosis in Oculina patagonica - a Mediterranean coral remarkable for its ability to survive long periods without algal symbionts. Led by Shani Levy and @xgrau.bsky.social
rdcu.be/eLbaZ
Picture of an Oculina patagonica colony. Some of the individual polyps in the colony have a brown-yellow colour, indicating that they harbour symbiotic algae. Others are completely white and lack algae.
Close-up picture of symbiotic Oculina polyps.
Hot off the press! Our latest work on the evolution of facultative symbiosis in stony corals, focusing on a remarkable Mediterranean species: Oculina patagonica.
🪸 🌊
#evobio #corals #coralbiology
www.nature.com/articles/s41...
Excited to share the preprint from my main postdoc project! It’s been a long journey—huge thanks to everyone who made it possible, especially @leticiarm1618.bsky.social for being the best collaborator one could ask for, and the amazing @kaessmannlab.bsky.social lab for the invaluable support!
BCA is a project to look out for — charting the diversity of cell type transcriptomes across the tree of life. Not only will it empower evolutionary studies, but also drive advances in biotechnology, biomedicine, and ecology. Kudos to the relentless, meticulous, and persistent team doing this work!
🚀 Check out our new review article “From Tiny Exons to Big Insights: The Expanding Field of #Microexons” now out in Annual Review of Genomics and Human Genetics!
doi.org/10.1146/annu...
Special thanks to @mirimiam.bsky.social, @crg.eu and @upf.edu!
Our study on a male-essential microRNA and the evolution of other dosage compensation mechanisms in birds is now out in Nature! www.nature.com/articles/s41...
A shout-out to people who made this possible: first and foremost @martaig.bsky.social and @arnausebe.bsky.social, but also @zolotarg.bsky.social @xgrau.bsky.social as well as all the ASP lab members, and of course @lukasmahieu.bsky.social @steinaerts.bsky.social and all the members of LCB in Leuven
We anticipate that applying the same approaches to other species of cnidarians and early-branching animals will enable comparative cell type analyses that will reconstruct evolutionary relationships of the major animal cell types and regulatory processes by which they first evolved.
To wrap up, here we pave the way for moving beyond conventional transcriptome-based cell type characterization in non-model species, by analyzing regulatory traits that define cell type identities in Nematostella, such as CREs sequence motif composition, active TFs, and GRN architecture.
Cell type relationships based on regulatory sequence similarity
We therefore show that effector gene usage groups functionally similar cell types, but regulatory features also reflect their ontogenetic relationships. E.g. GATA/Islet neurons show regulatory seq. similarities with
EMS and pharyngeal derivatives, and Pou4/FoxL2 neurons with ectodermal derivatives.
Finally, we explored cell type clustering using different features. We highlight transcriptionally similar retractor muscles, which share many access. genes, but have distinct sets of CREs bound by distinct TFs, and each clusters with the derivatives of their precursors (ecto. for TR and EMS for MR)
Motifs identified with deep learning in CREs of different cell types.
With invaluable help of @lukasmahieu.bsky.social and @steinaerts.bsky.social lab we trained deep learning sequence models to prioritize motifs predictive of cell type specific accessibility, and to uncover mostly flexible motif syntax in Nematostella, in line with billboard-like model of TF binding.
Cnidocyte gene regulatory characterization.
With that in hand, we characterized each cell type by usage of TF motifs, and then linked active TFs to their target genes in cell type specific gene regulatory networks (GRNs). We showcase cnidocyte GRN as an example and highlight important TFs with central roles in the network (FoxL2, Pou4, Sox2).
Correlation-based motif assignment approach.
The link between ATAC and RNA - from gene regulatory perspective - are TF binding motifs, which are not known for most Nematostella TFs. We devised a correlation-based approach to assign one motif to each TF, selected as best correlated among all motifs inferred by sequence similarity and orthology.
Alternative promoter of Gabra2 in neurons and muscle.
We used the atlas to characterize and quantify candidate CREs, including cell type-specific enhancers, cell type-specific promoters (SP), constitutive promoters (CP) and a smaller number of candidate alternative promoters (AP). We validated muscle and neuron AP of Gabra2 using transgenic reporters.
scATAC atlas of Nematostella vectensis.
To start, @martaig.bsky.social produced the first scATAC atlas for a non-model species, profiling 60k cells from adult and gastrula Nematostella vectensis - see it annotated in the app: sebelab.crg.eu/nematostella-cis-regulatory-atlas/ and the genome browser: sebelab.crg.eu/nematostella-cis-reg-jb2
In this project we wanted to extend cell type characterization in early-branching animals from transcriptome-based (scRNA) to regulatory-based definition, by experimentally profiling chromatin accessibility (scATAC) and computationally inferring TF binding to cis-regulatory elements (CREs).
I am very happy to have posted my first bioRxiv preprint. A long time in the making - and still adding a few final touches to it - but we're excited to finally have it out there in the wild:
www.biorxiv.org/content/10.1...
Read below for a few highlights...
Fixed! Thanks for pointing it out
Enhorabuena to my first PhD sibling 🥰
🧬🔍How can enhancers achieve tissue-specific activity?
We use MPRAs of synthetic enhancers to derive interpretable rules on TFBS arrangement 🚦 and discover that negative synergies drive specificity in hematopoiesis 🩸. Shoutout to @Robert Frömel & @larsplus.bsky.social for leading this work 🦹🦸.
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...
🧵
I’m very excited to share our work on the early evolution of animal regulatory genome architecture - the main project of my postdoc, carried out across two wonderful and inspirational labs of @arnausebe.bsky.social and @mamartirenom.bsky.social. www.nature.com/articles/s41...
We released our preprint on the CREsted package. CREsted allows for complete modeling of cell type-specific enhancer codes from scATAC-seq data. We demonstrate CREsted’s robust functionality in various species and tissues, and in vivo validate our findings: www.biorxiv.org/content/10.1...
"The main fates after gene duplication are gene loss, redundancy, subfunctionalization and neofunctionalization".
In our new review, @fedemantica.bsky.social and I argue we are missing the most prevalent one: specialization. And the same applies to alternative splicing! 1/7
tinyurl.com/45k7kbmp