Sergiu P. Pasca

article here: www.biorxiv.org/content/10.6...

Video above depicts responses to serotonin of neurons in human cortical organoids captured with the PsychLight2 sensor.

This work was led by a incredible group of scientists in lab: Sabina Kanton, Meng XiangLing, Chunyang Dong, Fikri Birey.

More needs to be done, but this is a first step toward understanding how neuromodulation shapes aspects of human development and disease.

The resulting neuromodulatory #assemboids allowed us to monitor serotonin release using genetically encoded sensors & its modulation of activity in cortical networks. We also used it to identify defects in assembloids from 22q11.2 deletion syndrome, and found that they can be modulated by SSRIs.

In this new BiorXiv preprint, we first generated #organoids containing neuromodulatory neuronal populations, including raphe nuclei-like neurons that produce and secrete serotonin, and then integrated them with cortical organoids.

This week we are introducing neuromodulatory assembloids.

Over the past few years, many circuits and cell-cell interactions have been modeled in assembloids, but these systems have not systematically incorporated neuromodulation.

Since then, she has been superbly applying it in her lab to ask questions about disease.

Such a joy to meet two of her enthusiastic lab members!

A great evening of bowling and discussions at the Packard ALS meeting in Baltimore this week.

So fun to meet lab alumni at conferences and watch how their own labs are thriving!

Really happy to see Jimena Andersen, now faculty at Emory University. When she was at Stanford, Jimena built 3-part #assembloids to study the corticospinal pathway

It is a privilege to join the Board of this organization committed to accelerating discoveries that accelerate our understanding and treatment of human disease by supporting fundamental research.

The latest @nature.com paper from Drs. @sergiuppasca.bsky.social and Daniel Geschwind's labs uses cortical #organoids to model #AutismSpectrumDisorder, and identifies how genetic risk can impact neurodevelopment.

🖇️ https://go.nature.com/4qZUzkS
🗨️ https://bit.ly/4thHuVG

I am happy to share our paper uncovering developmental convergence and divergence in autism spectrum disorder (ASD) using human stem cell models. This work was made possible through a wonderful collaboration with Sergiu Pasca’ lab @sergiuppasca.bsky.social and Daniel Geschwind’s lab.

Developmental convergence and divergence in human stem cell models of autism - Nature Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight in...

article here: www.nature.com/articles/s41...

This work was spearheaded by the heroic efforts of Aaron Gordon and Se-Jin Yoon, together with Lucy Bicks!

Still, this initial study illustrates how risk associated with genetically defined forms of ASD can propagate through transcriptional regulation, leading to convergent and divergent signaling defects.

This is just the beginning: we will need larger cohorts and more advanced cultures that capture cell diversity and interactions, such as #assembloids.

Interestingly, early time points harbored the largest mutation-specific changes, but distinct mutations converged on shared transcriptional changes as development progressed.

In this collaborative study with Dan Geschwind's lab, spanning almost a decade, we derived 96 hiPS cell lines representing 8 genetic ASD forms, idiopathic patients, and 20 controls, and after quality control differentiated 70 lines in > 150 experiments into human cortical #organoids for 100 days.

This week, we report in
@nature.com our effort to identify molecular convergence and divergence in #autism spectrum disorder (ASD) using human stem cell models.

Risk associated with genetically defined forms of ASD can propagate by means of transcriptional regulation to affect convergently dysregulated pathways @nature.com @sergiuppasca.bsky.social @stanforduniversity.bsky.social @dgsomucla.bsky.social
www.nature.com/articles/s41...

Experts met to discuss the ethics of using organoids in research Organoids are bits of neural tissue that model human brain development. Their use in science makes some uneasy, in part because the brain is so closely tied to our sense of self.

www.npr.org/2025/12/25/n...

A recent @npr.org piece by highlights the recent Asilomar meeting we organized on ethical considerations surrounding human stem cell models (#organoids & #assembloids and their transplantation), focusing on emergent questions and the potential to uncover new biology and therapeutics.

Audio below 👇

CRISPR screens in human neural organoids and assembloids - Nature Protocols This protocol combines pooled CRISPR–Cas9 screening with neural organoid and assembloid models and illustrates how it can be applied to map hundreds of disease genes onto cellular pathways and specifi...

Article here www.nature.com/articles/s41...

Work led by Meng XiangLing (now running her own lab at Baylor) with Noah Reis!

This is the 4th article in our series of detailed protocols describing the generation of regionalized neural organoids and of assembloids, and their transplantation, and it serves as a foundation for our hands-on course in our Stanford Brain Organogenesis Center

In our most recent publication in Nature Protocols, we outline detailed methods for performing CRISPR screens in neural #organoids and #assembloids.
The integration of these approaches is becoming increasingly powerful for uncovering human biology and gaining mechanistic insights into disease.

Applications closing at 6pm PT today!

Applications are pouring in for our international course on neural #assembloids taking place next spring on our beautiful Stanford campus

This is the LAST day to apply! No deadline extensions.

Please share 👇

Equally important, our meeting’s simple rule is holding throughout the sessions, with graduate students and postdoctoral scholars reliably asking the first 2 questions after each presentation.

A privilege to organize this with Sally Temple and Christine Mummery!

Next edition in December 2027!

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