The spatiotemporal dynamics of postnatal vascularization in the mouse brain Whole-brain tissue clearing and spatial transcriptomics were applied to map postnatal vascular development in the mouse brain, identifying three coordinated phases that link vascular growth to neurona...

The absolute dream paper for any #cerebrovascular developmental biologist !! Congrats to @nicolasrenier.bsky.social, @alexdubrac.bsky.social and their teams !

Very proud of our new paper, which I worked on in the @paquetlab.bsky.social for the past years! 👩‍🔬 Out this week in Science Translational Medicine @science.org. Find all the exciting details on what we found here 👇

None of this would have been possible without an amazing team, especially first author @angelikadannert.bsky.social and wonderful collaborators! Huge thanks to all co-authors and our funding sources! @synergy-munich.bsky.social @brightfocus.bsky.social @afi-ev.bsky.social @dfg.de Sanofi iAward 10/10

Can this model support translational applications?💊 A human Tau #PET tracer specifically bound to mutant 4R neurons. And we showed proof-of-concept that a drug, the aggregation inhibitor Anle138b, modulated our Tauopathy phenotypes. A human platform for #DrugDiscovery in #Tauopathies! 9/10

We also found synapse loss and ghost tangle-like structures in affected neurons, as well as nuclear lamina deformations linked to microtubule defects. These hallmarks mirror what is observed in patient brains with #Tauopathy. 8/10

Reproducing key late-stage hallmarks found in patient brain, affected neurons accumulated misfolded #Tau hyperphosphorylated at classical pathological epitopes, and formed tangle-like aggregates filling entire somata. All progressive, all cell-autonomous. 7/10

The 4R PLSF neurons developed seeding-competent, Sarkosyl-insoluble Tau that increased progressively over months. Electron microscopy suggested formation of fibril-like structures, confirmed as Tau-positive by immunogold labeling. 6/10

What would happen if only 4R was present? Exclusive expression of mutant 4R Tau disproportionately amplified pathology compared to neurons expressing 3R and mutant 4R Tau. At later stages, most neurons were affected. Spatial clustering analysis suggests inter-neuronal #TauSpreading in culture. 5/10

We combined 3R/4R #Tau expression with two synergistic Tauopathy mutations, P301L and S320F, that promote both nucleation and elongation of Tau fibrils. Neither 4R expression nor the mutations alone induced pathology. Only the combination triggered robust #Tauopathy. 4/10

One key reason: #iPSC neurons express the fetal 3R Tau isoform, but adult human brains have a 1:1 ratio of 3R and 4R. 4R is believed to be more aggregation-prone and central to disease. We used #CRISPR and PiggyBac to scarlessly induce adult-like #Tau splicing from the endogenous MAPT locus. 3/10

The problem: Despite extensive research, no human neuronal model reproducibly develops full late-stage #Tau pathology including seed formation, hyperphosphorylation and aggregation without transgenic overexpression or exogenous seeds. This limits study of disease mechanisms and #DrugDiscovery. 2/10

🧵New paper from the lab @isd-research.bsky.social @lmu-klinikum.bsky.social @lmu.de in STM @science.org! A human #iPSC-derived #Tauopathy model that endogenously develops late-stage Tau pathology. Free personal PDF: www.science.org/eprint/5H5YD....
Here's what we found👇 1/10

Big congrats to our PhD student @ishitaajith.bsky.social !!

FT ranking: Europe’s leading start-up hubs 2026 View the top centres providing business incubator and accelerator programmes

Munich takes the top two spots in the FT ranking of Europe’s startup hubs — UnternehmerTUM #1, Start2 Group #2.

Strong science, engineering depth, & real bridges between research + entrepreneurship. Huge opportunity ahead in part. for AI + bio/med. 🚀
www.ft.com/content/ab05...

Losing sleep over #iPSC transgene silencing after differentiation?
Same here.

Bright in iPSCs.
Gone after differentiation.

Our paper in @cp-cellstemcell.bsky.social maps what actually keeps expression on👇
www.cell.com/cell-stem-ce...
🔗 Free access (50 days):
www.sciencedirect.com/science/auth...

Many thanks @nature.com for selecting our image of a fully #iPSC derived #BBB (#blood-brain-barrier) as 'Image of the Week' in Nature Briefings: mailchi.mp/nature/trans... 😀 Find the image in action in our primary research paper here: rdcu.be/eUIl3

Image of the Week: Congrats to the team of González-Gallego J et al., Nat Neurosci. 2026 for this lovely award in Nature Briefing 🏆 🖼️ @judit-gonzalez.bsky.social @paquetlab.bsky.social (->Fig 2b www.nature.com/articles/s41...)

🏛️ 200 Years of LMU in Munich 🎓 Founded in 1472, relocated from Landshut to Munich in 1826 — today LMU celebrates 200 years in Munich and inaugurates Prof. Dr. Matthias H. Tschöp as President.

Our paper is (finally) out in Cell today!

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
www.cell.com/cell/fulltex...

Great collaborative effort - read more from first author @asamelson.bsky.social below:

Infotafel mit Logo der Prospects DFG Research Career Series und den Terminen: 10.02.2026, 14:30 - 16:00 Uhr – The Emmy Noether Programme (in English) 11.03.2026, 10:30 - 12:00 Uhr – DFG-Förderangebote für Postdocs 14.04.2026, 14:30 - 16:00 Uhr – Das Walter Benjamin-Programm 20.05.2026, 14:00 - 15:30 Uhr – DFG funding Opportunities for Postdocs (in English) 25.06.2026, 14:00 - 15:30 Uhr – The Emmy Noether Programme (in English)

#ECR save the dates! 🗓️ In der Reihe #PROSPECTS informiert unser Team #Karriereförderung auch 2026 regelmäßig über die Fördermöglichkeiten bei der DFG. Hier haben wir die Infotalks für die erste Jahreshälfte. Teilnahme ohne vorherige Registrierung möglich, Link erscheint hier.
👉 sohub.io/bvv0

China’s ‘Dr. Frankenstein’ Thinks Time Is on His Side

The reckless human embryo genome editor, He Jiankui, known as China's Dr. Frankenstein, is back at it.
"People were not yet ready to accept what I was doing."
We're still not.
nytimes.com/2026/01/13/w...

Stem Cell Reports is calling for applications to serve on its editorial team as an Early Career Editor, a prestigious opportunity for outstanding, early-career scientists to help shape the future of stem cell publishing. The deadline to apply is 13 March 2026. https://ow.ly/8iiP50XWscj

🧠 Fully human #iPSC - derived 3D #BBB model with perfusable vessels and key BBB functions. #FOXF2 deletion causes BBB dysfunction, rescued by lipid-nanoparticle delivery of Foxf2 mRNA.

🔗Read a summary of the study on our website: www.synergy-munich.de/news-events/...

Many thanks #Alzforum for featuring our recent studies on iPSC models of the #blood-brain-barrier! And we are also grateful for all the thoughtful comments from experts in the field! www.alzforum.org/news/researc.... Primary papers can be found here rdcu.be/eUIl3 and here rdcu.be/eUImz 🙂

PS: If you interested in this kind of work, we are looking for a highly motivated Postdoc to continue in this area of the lab. See our profile and webpage for more details: isd-research.de/paquetlab

This was a great collaboration! Many thanks to all authors, especially @judit-gonzalez.bsky.social and @katvolgyi.bsky.social, as well as our funding sources! @dfg.de @synergy-munich.bsky.social BMBF @ec.europa.eu and the Foundation Leducq network www.brenda-leducq.de !!! 7/7

Lastly, treatment with AKB-9778, which boosts Tie2 activity by blocking Tie2-dampening vascular endothelial protein tyrosine phosphatase, restored Tie2 signaling both in mice and human endothelial cells, which rescued nitric oxide production and had positive effects on infarct sizes in mice. 6/7

We also found that FoxF2 in endothelial cells facilitated functional hyperemia and limited infarct size in adult mice, again mediated via Tie2 signaling and underscoring the role of FOKF2 in #Stroke and #Small vessel disease. 5/7

In both EC-specific KO mice and our new fully iPSC-derived BBB model (see here: rdcu.be/eUIl3), loss of FOXF2 caused BBB leakage and attenuated TIE2 signaling, pointing to a central role of this pathway in FOXF2-dependent BBB regulation. 4/7

By performing ChIP-seq and omics in complementary mouse and human iPSC-derived models of FOXF2 deficiency we found that FOXF2 acts as a transcriptional activator of Tie2 and other lineage-specific genes in endothelial cells. 3/7