Here's some background on our latest paper on morphogen patterning of human neural organoids!

... with special mention to our amazing collaborators @kirkebylab.bsky.social Gaurav, Pedro and Charlotte 🙌

Congratulations 👏 and huge thanks to all the authors for your essential contributions to this manuscript @akanksha-jain.bsky.social
@zhisonghe.bsky.social @jasperjanssens.bsky.social @josch1.bsky.social Ryoko, Gosia, Makiko and Benedikt...

We’re so excited to share this work with the community🎉 and hope it can be used to optimise the design of the next generation of neural organoid models 🧠🧫

Something we’re particularly excited about is the co-development of neural and non-neural tissues in some of our conditions 🧩

Fine-tuning these morphogen conditions and using the right patterning modalities could help us develop more complex organoids 🏗️🏙️

Most variability came from differences between hPSC lines and neural induction strategies, not batch or sex🧐

Dual SMAD inhibition enriched for CNS fates but was much less reproducible than minimal neural induction (without SB+Noggin) across lines🔥

Some regulons were consistent across cell lines👱🧑‍🦰🧑‍🦱 and neural induction media🧫, but others varied strongly!

This gives us an idea of which cell types may be easier or harder to achieve reproducibly in vitro 🧪☑️

By sampling organoids right after morphogen exposure, we could quantify activation of patterning regulons - signals we usually lose as neural progenitors disappear in older organoids 🫣

We sampled early-stage organoids to capture a rich spectrum of developmental states, from PSCs to neurons 👶➡️🧑

Our population of interest was the neural progenitors undergoing patterning🐣, which nicely complements other datasets focusing on more mature neuronal identities 🧠

CellFlow enables generative single-cell phenotype modeling with flow matching High-content phenotypic screens provide a powerful strategy for studying biological systems, but the scale of possible perturbations and cell states makes exhaustive experiments unfeasible. Computatio...

We also designed a reproducibility screen: 12 morphogens across 4 hPSC lines, 2 neural induction media and 2 technical batches 💪

Our systematic datasets are ideal for modeling approaches 💻 like CellFlow www.biorxiv.org/content/10.1...

We used SHH, WNT, FGF8, RA, and BMP4/7 pathway modulators to probe, in an unbiased way, how morphogen timing 🕑 concentration 📶 and combinations🌀affect patterning outcomes.

For each morphogen, some factors matter more ➕ and others less➖!

Aware of the hurdles, we tried to put an end to this suffering 🙅‍♀️

Pipette in hand, @nazbukina.bsky.social and I set out to screen for as many factors as we could to better understand how early regional patterning works in human neural organoids 🧠🧫

We usually focus only on the "best" conditions⭐️ ignoring what happens beneath the surface: batch effects, mixed identities, heterogeneity 🥴

‼️What if, instead of avoiding it, we harnessed that heterogeneity to build more complex organoid systems?

All regionalised organoid protocols rely on the same morphogens 🪅 SHH, RA, BMPs, FGFs, WNTs 🪅 applied at different doses and times. Each lab painstakingly optimises conditions to generate the purest CNS region-specific populations.

A summary schematic showing morphogen gradients in the developing human embryo, an overview of two screenings performed in the study (one testing factors related to patterning conditions, another one testing factors related to patterning reproducibility) and icons representing the main readouts of the screenings: organoid cell type composition, measures of morphogen interactions, primary atlas comparison and regulon activity.

Your new batch of cortical organoids resulted in mixed regional identities closer to hindbrain. Why is patterning so hard?😩

✨Our latest paper might help you✨
tinyurl.com/neorgpat

#morphogen #neuralorganoids #patterning #scRNAseq
@graycamplab.bsky.social @ethz.ch @nazbukina.bsky.social

Induction of menstruation in mice reveals the regulation of menstrual shedding During menstruation, an inner layer of the endometrium is selectively shed, while an outer, progenitor-containing layer is preserved to support repeated regeneration. Progress in understanding this co...

I’m thrilled to share my postdoc work and the first paper from the McKinley Lab! 🎉
@karalmckinley.bsky.social
We built the first transgenic model of menstruation in mice.
We used it to uncover how the endometrium organizes and sheds during menstruation. 🧪
www.biorxiv.org/content/10.1...
🧵