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Reposted by Teresa Rayon

Philip Ball @philipcball.bsky.social · 5d

We can identify genetic associations with disease, but the hard part is figuring out what effects the variants at those loci actually do, including how penetrant they are. This is hard. But one phrase in this piece struck me in particular... /1
www.science.org/doi/10.1126/...

Penetrance and variant consequences—Two sides of the same coin?

To get more out of genome sequences, the effects of variants need to be quantified

www.science.org

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Teresa Rayon @trayon.bsky.social · 10d

If you’re interested in this topic, please also check out @ebisuyamiki.bsky.social ky.social’s preprint.www.biorxiv.org/content/10.1...v2

Systematic differences in protein stability underlie species-specific developmental tempo

Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model to study interspecies differences in developmental tempo, as its oscillation period in hu...

www.biorxiv.org

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Teresa Rayon @trayon.bsky.social · 10d

Collectively, we report species-specific differences in protein production and degradation rates and provide *in vivo evidence* that degradative machineries are less active in human embryos than in mice. Finally, we establish a causal role for protein degradation on dev. tempo.

👇👇

Protein degradation shapes developmental tempo in mouse and human neural progenitors

The pace of embryonic development differs markedly across mammalian species, yet the molecular mechanisms underlying these tempo differences remain largely unknown. Here, we systematically compared pr...

www.biorxiv.org

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Teresa Rayon @trayon.bsky.social · 10d

To test if we could accelerate differentiation tempo as well, we targeted the degradation of IRX3 via Halo tagging + HALO-PROTAC and show it accelerates OLIG2 expression.

So, we demonstrate that modulating protein stability can influence the expression of a downstream TF.

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Teresa Rayon @trayon.bsky.social · 10d

To test causality, we inhibited proteasomal activity.
Three day treatments with proteasomal inhibitors mostly killed the cells, BUT we observe signs of differentiation deceleration

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Teresa Rayon @trayon.bsky.social · 10d

This meant that degradative machineries may be in charge:
✔️ differential abundance & stability of proteasomal particles
✔️ higher proteasomal activity in 🐭 compared to 👤 embryonic spinal cord

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Teresa Rayon @trayon.bsky.social · 10d

Proteins with multiple molecular functions show this trend, and this is true for proteins in different subcellular locations as well.

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Teresa Rayon @trayon.bsky.social · 10d

But which specific proteins show differences in stability? We confirm that most of the proteins indeed are more stable in human than in mouse as measured by SILAC proteomics. And this is also true for 1:1 homologous proteins (3402 proteins!).

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Teresa Rayon @trayon.bsky.social · 10d

Next, we compared protein abundance. We find selective upregulation of proteins related to degradation & mitochondrial metabolism in the 🐭. This was cool, as differential abundance was associated to a subset of functions that may explain the differences in stability!

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Teresa Rayon @trayon.bsky.social · 10d

We also found ~2-fold difference in global rates of production in 🐭 vs 👤. So, rates of protein production + degradation are species-specific.

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Teresa Rayon @trayon.bsky.social · 10d

First, we generated knock-in OLIG2-SNAP tagged mouse and human ESCs and measured OLIG2 turnover.
We find ~1.4-fold difference in decay and little differences in OLIG2 production. We also observed higher OLIG2 production rates in mouse.

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Teresa Rayon @trayon.bsky.social · 10d

Collaborative effort led by @Sotha Nakanoh & Despina Stamataki, with valuable contributions from Rayon & Briscoe lab members, as well as support from the proteomics teams (Crick & BI) and the BI bioinformatic team 🥂

Protein degradation shapes developmental tempo in mouse and human neural progenitors

The pace of embryonic development differs markedly across mammalian species, yet the molecular mechanisms underlying these tempo differences remain largely unknown. Here, we systematically compared pr...

www.biorxiv.org

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Teresa Rayon @trayon.bsky.social · 10d

We've updated our first #preprint from the lab! A collaboration with @jamesbriscoe.bsky.social

🔥 now including in vivo 🐭&👤 embryo data

www.biorxiv.org/content/10.1...

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Reposted by Teresa Rayon

The Loke Centre for Trophoblast Research @loke-ctr.bsky.social · 12d

Today we celebrate the life and legacy of Bob Edwards, pioneer of IVF, welcoming over 200 visitors for a two part event to mark what would have been his 100th birthday! Read more at www.cam.ac.uk/research/new...

Cambridge marks centenary of IVF pioneer Sir Robert Edwards’ birth

Celebrations at the University of Cambridge honour the life, work and legacy of Sir Robert Edwards, whose work revolutionised fertility treatment through the

www.cam.ac.uk

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Teresa Rayon @trayon.bsky.social · 19d

Such a hard question to ask, and beautiful work showing cell-specific dependencies 🤯. Love it!! Congrats!!!!

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Reposted by Teresa Rayon

Development @dev-journal.bsky.social · 20d

Excited for the #CSHAmeeting on Human Development - From Embryos to Stem Cell Models in Suzhou, China? Our Editor, Peter Rugg-Gunn, is attending and has curated a collection of review-type and Research Articles on this topic: journals.biologists.com/dev/collecti...

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Reposted by Teresa Rayon

Vinca Yadav / विंका यादव @whyvinca.bsky.social · 26d

On the train back now from the 2nd ever #EMBODevMet, where I got to see many familiar faces, meet new people, and hear about lots of great and inspiring work combining two of my top scientific interests (development & metabolism) in so many different systems! 🤓🤩

EMBL Events @events.embl.org · 26d

✨ That's a wrap on #EMBODevMet after four inspiring days of cutting-edge science, new ideas, and reconnections.

👏 A huge thanks to all participants, speakers, and organisers who made this event so special.

We can't wait to welcome you back to another EMBL event 👉 embl.org/events

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Teresa Rayon @trayon.bsky.social · Sep 4

Such great news, well done!!!! 🐠🌡️🐟⏳

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Reposted by Teresa Rayon

Oliver Harschnitz @harschnitz.bsky.social · Sep 3

Beautiful work from Nan Xu and the @studerl.bsky.social lab in @natcellbio.nature.com combining directed differentiation of hPSCs and genome-wide CRISPR screens to identify the epigenetic factors Menin and SUZ12 as regulators of developmental pace across germ layers.
www.nature.com/articles/s41...

Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing - Nature Cell Biology

Xu et al. perform a whole-genome CRISPR-Cas9 knockout screen using directed differentiation systems. They find that MEN1 and SUZ12 modulate human developmental timing by epigenetically controlling biv...

www.nature.com

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Teresa Rayon @trayon.bsky.social · Sep 3

Congrats to authors on this preprint!🦈 brains, what’s not to like?

*Deep conservation in brain basal progenitors. Cool!

Idoia Quintana-Urzainqui @idoiaeu.bsky.social · Sep 2

Short answer: YES! We identified a mitotic cell state in sharks that matches mouse basal progenitors both transcriptomically and anatomically. While we found key similarities, some differences hint at unique evolutionary paths in sharks and mammals. For a deeper dive, check out the full paper!

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Reposted by Teresa Rayon

Dirk Benzinger @dbenzinger.bsky.social · Aug 27

Super excited that our latest work is out!

We use optogenetics to dynamically control and study the formation of morphogen gradients.

If you are interested in optogenetic tools and/or how cells shape and process extracellular signals, check out @jamesbriscoe.bsky.social's thread and the paper.

James Briscoe @jamesbriscoe.bsky.social · Aug 26

Our latest: We developed a chemo-optogenetic system for precise spatiotemporal control of morphogen production. Using dual light + small molecule control of Sonic Hedgehog production, we recapitulated neural tube patterning in vitro & measured spread of Shh

🧵

www.sciencedirect.com/science/arti...

Investigating morphogen and patterning dynamics with optogenetic control of morphogen production

Morphogen gradients provide the patterning cues that instruct cell fate decisions during development. Here, we establish an optogenetic system for the…

www.sciencedirect.com

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Teresa Rayon @trayon.bsky.social · Aug 27

🔥🔥🔥🔥🔥 congrats!!!!! 🎉

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Reposted by Teresa Rayon

Joaquina Delas @joadelas.bsky.social · Aug 21

Read more about @sermenchero.bsky.social 's work in this PNAS Journal Club. #opossums!

Proceedings of the National Academy of Sciences @pnas.org · Aug 21

In #opossums and other #marsupials, #GeneExpression follows familiar rules, but at an unusual pace. In PNAS Journal Club: www.pnas.org/post/journal...

#DevelopmentalBiology #evolution #embryo #transcriptome

The arms and heads of opossums (pictured here one day before birth ) and other marsupials develop faster than their legs and back bodies.
Image credit: Sergio Menchero Fernandez/ Francis Crick Institute, London.

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Teresa Rayon @trayon.bsky.social · Aug 17

Why would anyone want to be a scientist? 👩‍🔬

Very much enjoyed this piece. Of course there may be other reasons, but these resonate well with me.

A reminder for all of us that I find rarely mentioned: “Great work becomes part of the background”

Richard Sever @richardsever.bsky.social · Aug 15

"why [would] anyone intelligent enough to be a scientist choose to be one [given] the unfavorable risk-to-reward ratio "?

One of the most intelligent people you could meet offers some answers: having ideas, watching them develop, and sharing them journals.biologists.com/jcs/article/...

Why would anyone want to be a scientist?

It is difficult to fathom why anyone intelligent enough to be a scientist would actually choose to be one. Doing good science requires the utmost exertion of body, mind and spirit, yet is consistently...

journals.biologists.com

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Reposted by Teresa Rayon

Stefan Schoenfelder @stefanschoenfelder.bsky.social · Aug 8

“Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.”
Great paper and very important finding - many congrats Axel & team! 👏👏

Axel Visel @axelvisel.bsky.social · Aug 8

Enhancers are "just DNA" - finding all of them in the genome is hard.

www.nature.com/articles/s41...

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