🇲🇽 Ex utero embryogenesis and stem-cell embryo models. 1st gen scientist. Group Leader at 4DCP, HHMI Janelia, USA.

Ashburn, VA
Joined March 2011
Thanks to MIT Technology Review for selecting me as one of the 35 innovators under 35 for 2024!
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Alejandro Aguilera Castrejon retweeted
🎉 Our paper is out today in @ScienceMagazine! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @HiromuneEto & @jddeleede! 🔗 science.org/doi/10.1126/scie…
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Alejandro Aguilera Castrejon retweeted
Embryo, is the story of how one cell becomes millions that build a body within which a #HumanBeing emerges gradually—one cell at a time. It explores the origin of human nature and what #IVF, #EmbryoModels & artificial wombs mean for our future. amazon.com/Embryo-Becoming-A…
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Alejandro Aguilera Castrejon retweeted
An aptly titled paper shows, for the first time, the significance of heterogeneities of gene expression in the construction of complex systems : fate decisions are group decisions. Previously @biorxivpreprint cell.com/cell/fulltext/S0092… #MustRead @Jshendure lab
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Alejandro Aguilera Castrejon retweeted
Exciting day for DNA Typewriter w/ 2 papers from the lab & SeaHub out today :) 1. Mouse lineage from E0 to E13.5 science.org/doi/10.1126/scie… 2. A fluctuation test for gastruloid heterogeneity cell.com/cell/fulltext/S0092… Paper #1 covered in quoted thread. More on paper #2 here. 1/n
Thrilled to post thread re: new single-cell lineage of mouse embryo reconstructed w/ DNA Typewriter. One animal, zygote to late organogenesis (E13.5). Tree has 1,340,794 transcriptionally profiled, annotated tips (cells), 1,142,588 dated internal nodes, rooted at zygote 1/n
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Alejandro Aguilera Castrejon retweeted
Peter Hegemann and Georg Nagel – awarded the 2026 medicine prize – discovered a remarkable protein, channelrhodopsin, in a single-celled alga. Hegemann wondered how Chlamydomonas, a single-celled alga, is able to swim towards a light source. In the early 2000s, he and Georg Nagel discovered channelrhodopsin, an algal protein with unique properties, found on the surface of the cell. When it is illuminated by blue light, a channel opens through the protein. Charged ions then flow into the cell, creating an electrical impulse. They found that regardless of which cell they put the protein in, those cells became light sensitive. #NobelPrize
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Alejandro Aguilera Castrejon retweeted
BREAKING NEWS The 2026 #NobelPrize in Physiology or Medicine has been awarded to Karl Deisseroth, Peter Hegemann and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.”
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Alejandro Aguilera Castrejon retweeted
Today our lab is excited to share a new study in Cell: “Non-invasive control of gene editing in vivo by photoswitchable Cas12f and focused ultrasound.” We engineered a compact CRISPR system that can be activated at specific locations in the body using focused ultrasound (🧵)
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Alejandro Aguilera Castrejon retweeted
This isn’t just anecdotal. I scraped bibliometric data from Nobel laureates and computed the disruption index of their top papers from each 5-year bin of their publication records. Disruptiveness declines ~linearly with age!
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Alejandro Aguilera Castrejon retweeted
Two years since the 1st submission, our work on limb heterochrony is finally out! 🎉🎊@CellCellPress Delayed hindlimb dev vs forelimb is a widely conserved trait in mammals. We show that maternal O2 regulates this phenotype 👉🏻 shorturl.at/MGrwl
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Alejandro Aguilera Castrejon retweeted
As someone who did this kind of genome mining work during my PhD, some thoughts on this Anthropic announcement: First, the very simplified version of what they did is that they noticed two genes (one known, one new) sitting next to a weird repeating piece of DNA. More specifically, they described an unusual reverse transcriptase (RT) associated with a repetitive DNA array and an unknown accessory protein. This kind of process was used to understand CRISPR back in 2002 and was key to the gene editing tools we use today. To put this into context, though, people have been finding RTs associated with CRISPR arrays since 2008, and this general kind of genome-neighborhood mining has been used to discover new biological systems for decades. The basic genome-mining strategy is well established, and there are now mature tools and published pipelines for doing much of this. There are papers that discover and experimentally validate dozens of new systems using this approach in a single study. Doing it in bacteriophage genomes is also nothing new (eg CasPhi). Finding a weird cluster of genes and repeats is often the easy part. The hard part, and where the real discoveries come from, is figuring out what the system actually does. Eg for the bridge-RNA discovery in 2024 from @arcinstitute or the discovery of CasPhi in 2020 from @DoudnaJennifer they figured out the pieces of the system and the rules for what makes it work so it can be used. Anthropic does not yet know what this does. They’ve shown that the repeat array produces RNAs, but not what those RNAs do, what the RT does with them, or whether the system has any of the programmable properties that make the CRISPR comparison justified. I’m genuinely rooting for all of the frontier labs to seriously get into biological discovery, and I’m excited about what comes out of it. But announcing these very early, incremental findings with the framing of a major discovery doesn’t help. I’d much rather they set the bar high now, so that when an AI actually discovers a fundamentally new biological mechanism, everyone appreciates how big a deal it is.
Claude has discovered a previously unknown enzyme system hidden in the DNA of bacteriophages. Beside the enzyme’s gene sits a long array of repeating DNA—a structure that looks somewhat similar to CRISPR. We don’t yet understand what this system does, but only a handful of known systems share its features, and all of them are able to cut, copy, and paste DNA. Historically, the discovery of such programmable systems has helped revolutionize medicine. CRISPR, for instance, is now the foundation of genetic medicines. But it will take much more work to learn what this system does, and whether it can be put to similar use. Read more: anthropic.com/news/claude-di…
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Alejandro Aguilera Castrejon retweeted
Science – debatably the #1 journal in the world – published a paper on a "virtual biotech" AI system this week but the authors never even test if it works well! all the evidence for its performance is 3 anecdotes the paper has no benchmark scores, no baselines, no replicates
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Alejandro Aguilera Castrejon retweeted
Today in @Nature, we report a new approach to studying human brain development and modeling disease in vivo. Human neural #assembloids and #organoids have opened new ways to study development in vitro, but they also have important limitations. Transplantation can provide a more physiological environment, yet human cortical cells then develop within a rodent brain that matures much faster, constraining their growth and integration. To address some of these limitations and obtain more advanced functional readouts relevant to disease biology, we generated #apallial mice, in which ~98% of the cortex and hippocampus fail to form, creating space for transplanted human cortical organoids to grow and integrate extensively. We call these #xenocortical mice (XCX). Nearly 7 years in the making. Congratulations to an extraordinary team and wonderful collaborators! Link to the article below 👇
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Alejandro Aguilera Castrejon retweeted
Abdelbaki, A., McCarthy, A., Karsa, A. et al. Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors. Nat Biotechnol 44, 1482–1492 (2026). doi.org/10.1038/s41587-025-0…
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Alejandro Aguilera Castrejon retweeted
First preprint from the lab, led by @rantinggev! We identify a metabolic bottleneck that helps set the pace of human development: low levels of the redox enzyme GPD1L limit NADH recycling. Boosting GPD1L mimics mouse cells and accelerates development! biorxiv.org/content/10.64898…
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Alejandro Aguilera Castrejon retweeted
1/11 Our newest study asks how far cellular reprogramming extends in the ordinary course of animal life. Metamorphosis offers the test of maximal severity: the wholesale conversion of one body plan into another. Out now in Nature Communications. nature.com/articles/s41467-0…
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Alejandro Aguilera Castrejon retweeted
Thrilled to post thread re: new single-cell lineage of mouse embryo reconstructed w/ DNA Typewriter. One animal, zygote to late organogenesis (E13.5). Tree has 1,340,794 transcriptionally profiled, annotated tips (cells), 1,142,588 dated internal nodes, rooted at zygote 1/n
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Alejandro Aguilera Castrejon retweeted
New Toettchlab paper alert! Harrison Oatman just published his beautiful work combining software design for "smart" microscopy+optogenetics and some really beautiful work understanding EGFR-driven collective cell migration. cell.com/cell-systems/fullte…
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Alejandro Aguilera Castrejon retweeted
This is not AI. This is real microscopy! 🔬 An intact gut, rendered transparent and imaged in 3D using light-sheet microscopy! 🤓 Looking inside organs to investigate where pathogens, immune cells, or disease processes may persist. #LongCovid #FluorescenceFriday
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Alejandro Aguilera Castrejon retweeted
We’re looking to recruit a postdoc to work on developing genomic language models. We’ve been spending the last few years developing new multimodal sequencing methods for sequencing and assembling new genomes (paper soon) — the ultimate pretraining data. Email me at [email protected] if interested
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