Multi-organ transcriptomic aging atlas in killifish, with both males and females! 🐟🐟🐟
Huge congratulations to Emma, Jing, Tony and the entire team!! ✨⭐
@emkcosta.bsky.social
@jingxunchen.bsky.social
Wyss-Coray lab!
www.nature.com/articles/s43...
Online now! Costa, Chen et al. performed RNA-seq on 13 tissues, six ages in male and female African turquoise killifish. The Killifish Aging Atlas provides a comprehensive resource for aging studies. @emkcosta.bsky.social @jingxunchen.bsky.social @brunetlab.bsky.social
doi.org/10.1038/s435...
Congratulations to the entire team and a huge thank you to all collaborators! Thank you so much for the support of the Knight Initiative for Brain Resilience at Stanford for this project! 🙏
We are excited by this study because it provides the potential for 'immunotherapies' for the old brain.
Of course, a lot remains to be done, including identifying additional efficient 'immunotherapies' that can rejuvenate old brain function.
More broadly, this IL-10 variant has beneficial effects on cognitive behavior (done with Saul Villeda's lab) in old mice.
This suggests that quenching inflammation in old brains can boost cognitive function in old individuals
Importantly, this IL-10 variant decreases inflammation in both neurogenic niches in the adult brain – the subventricular zone and the dentate gyrus.
The IL-10 variant has a small beneficial effect on the production of new neurons from the subventricular zone neurogenic niche in old individuals.
We found that this engineered IL-10 variant reduces inflammation in microglia (and does not trigger strong T cell activation) in old brains.
We chose IL-10 because we noticed that the IL-10 pathway is going down with age, notably in microglia.
We infused this engineered IL-10 variant that is more targeted toward anti-inflammation into old brains and examined its impact using a variety of assays.
So could age-dependent inflammation be quenched to counter brain aging?
For this, we used an engineered cytokine (IL-10) which has anti-inflammation properties and was generated by Bobby Saxton in the Garcia lab.
We found that infusing this checkpoint inhibitor into the brain triggers massive inflammation of microglia.
This suggests that reversing T cell exhaustion actually augments inflammation in the aged brain (which is already more inflamed than the young brain), which is likely detrimental.
We wondered what would happen if we infused a checkpoint inhibitor into the aged brain to reverse this T cell exhaustion.
We used a potent checkpoint inhibitor (RIPR-PD1) engineered by Ricardo Fernandes in the Garcia lab, and we examined its effect on a key brain region – the subventricular zone.
We and others had previously observed that cytotoxic T cells strikingly accumulate in the old brain.
Characterizing T cells from aged brains, we noticed that some of them have hallmarks of memory T cells whereas others have hallmarks of exhausted T cells, such as the checkpoint protein PD1.
Brain aging is associated with cognitive decline and a dramatic increase in neurodegenerative diseases, including Alzheimer's disease.
Could 'immunotherapies' – strategies based on the immune system – counter brain aging?
Excited to share our new study using engineered immune proteins to quench inflammation in aged brains!!
Congratulations to Paloma Navarro and the entire team!
Fantastic collaboration with Chris Garcia's lab, Tony Wyss-Coray's lab, and Saul Villeda's lab!
www.cell.com/immunity/ful...
We have posted a Research Assistant (LSRP1) position to work on aging and 'rejuvenation' using mouse models!! 🐭
careersearch.stanford.edu/jobs/life-sc...
Apply and join our awesome lab!! (please share) 😎
Interested in the mechanisms of aging and 'rejuvenation'?
Our lab at Stanford has a Research Assistant/Lab manager position open!!
Apply and join our awesome team! 😎 (please share)
careersearch.stanford.edu/jobs/life-sc...
New episode (1211), with Dr. Coleen Murphy (@ctmurphy1.bsky.social). We talk about her book, How We Age: The Science of Longevity. #Biology #Science
YouTube: youtu.be/Fy22JhtHhdU
Podcast: bit.ly/4a1fCh8
We are hiring!! Lab Assistant II position to work with the killifish! 🐟🐟🐟 This is an amazing model to study aging and 'suspended animation'
careersearch.stanford.edu/jobs/lab-ass...
Come and join our fantastic team at Stanford!! 🤩 Please share!
Join us for an awesome Keystone Symposia in Banff, Canada in March 2026! Fantastic line up of speakers at the juncture between immunity and aging!! www.keystonesymposia.org/conferences/...
📣 Deadline extension for #EMBOBrainEpi!
Good news for anyone who did not submit an abstract for the EMBO Workshop 'Brain (epi)genome': the abstract deadline is now 26 January 👉 s.embl.org/brg26-01-bl
Join us to explore how genome and epigenome shape brain cell diversity, function, and disease 🧠
I'm just delighted to announce our new preprint on genome-scale perturb-seq in CD4+ T cells. We learned both general lessons about the power of perturb-seq, and specific lessons about T cell biology.
Led by amazing postdocs Emma Dann and Ronghui Zhu, with my wonderful collaborator Alex Marson.
We have had a lot of requests for the protocol for single-nucleus RNA-seq of adult C. elegans neurons that our lab developed - I hope that you find this helpful! 🧪 #Celegans www.sciencedirect.com/science/arti...
New paper alert!!...🤩 Led by @blogeman.bsky.social, we identify how cell type-specific hormonal responses in the hypothalamus tunes parenting behavior in males and females 🐭🧠🍼. Highlights in thread 👇 1/6
www.biorxiv.org/content/10.6...
Remarkable energy at the inaugural @cshlnews.bsky.social conference on Assembloids and complex cell–cell interactions across tissues and systems
A wonderful series of talks so far highlighting advances & discoveries being made with these self-organizing systems and a few common themes are emerging
Our latest collaboration with @jkpritch.bsky.social – led by joint post-doc Mineto Ota – is in @nature.com today: www.nature.com/articles/s41...
I am thrilled to share our latest work led by @zurisullivan.bsky.social in collaboration with @moffittlab.bsky.social ! We find that the brain encodes distinct, pathogen-specific sickness states across behavior, physiology, neural activity, and gene expression 1/6
www.biorxiv.org/content/10.6...
Top left: Schematic derived from WormPaths showing methionine salvage and arginine-derived metabolic pathways. Information regarding gene level and H3K4me3 status from Control, sams-1 or sams-4 animals in basal or heat-shocked conditions is marked in legend. Data is from Godbole and colleagues eLife 2023. Bottom left: Schematic showing connections between SAM and PC synthesis to trafficking of PC to and within the mitochondria. Right: Transmission electron micrograph of normal mitochondria (blue, top) compared to those with low levels of the phospholipid phosphatidylcholine (pink, bottom) from C. elegans intestinal cells, showing collapse of the mitochondrial network and accumulation along the intestinal lumen. Image taken by Dr. Maria Ericsson
S-adenosylmethionine synthases (SAMS) have distinct roles in #StressResponse & #mitochondrial metabolism in #Celegans. @akw-lab.bsky.social &co show that SAMS-1 supports broad metabolic functions (e.g. PC synthesis), while SAMS-4 aids protein transmethylation @plosbiology.org 🧪 plos.io/4rvQvtt
Interested in neural stem cells and neurogenesis throughout lifespan?
Exciting meeting in 2026 in Switzerland!!
neuro-unige.ch/news/csf-mee...
Congratulations Elphège!! 🤩🥂
Here is a copy of last year's Twitter thread explaining our preprint - jump to (21) for the new stuff 👀
Synergy between cis-regulatory elements can render cohesin dispensable for distal enhancer function
now revised and journal accepted at www.science.org/doi/10.1126/...
🧵👇
