Today, our xenocortication work is on the cover of @Nature! accompanied by the Editorial and a News & Views (links 👇) Huge congratulations to our four co-first authors: @KaganovskyNeuro, @kevinwkelley (now Assistant Professor), Tilo Gschwind and Paul Harary, and to the entire team, including our close collaborators Brian Wandell, Julia Kaltschmidt, Ivan Soltesz and @KarlDeisseroth. #Xenocortex #Organoids #Neuroscience

Such an amazing day here at @Stanford as @KarlDeisseroth, our colleague in the Department of Psychiatry, received the @NobelPrize! A wonderful mentor, generous colleague and, above all, a dear friend. Amid all the craziness this morning, I managed to catch him in our Clark building @StanfordBioX wearing his (now) iconic shirt!

Today in @Nature, we report a new approach to studying human brain development and modeling disease in vivo. Human neural #assembloids and #organoids have opened new ways to study development in vitro, but they also have important limitations. Transplantation can provide a more physiological environment, yet human cortical cells then develop within a rodent brain that matures much faster, constraining their growth and integration. To address some of these limitations and obtain more advanced functional readouts relevant to disease biology, we generated #apallial mice, in which ~98% of the cortex and hippocampus fail to form, creating space for transplanted human cortical organoids to grow and integrate extensively. We call these #xenocortical mice (XCX). Nearly 7 years in the making. Congratulations to an extraordinary team and wonderful collaborators! Link to the article below 👇

We are building a new translational effort at @Stanford focused on advancing therapies for severe neuropsychiatric disorders. We are recruiting an Executive Director to help shape this initiative across @StanfordMed and Lucile Packard Children’s Hospital. This is an exciting opportunity to work at the intersection of neuroscience, therapeutics, and clinical translation. More on this effort soon! Please share with anyone who might be a great fit!

This week we welcome here at @Stanford a remarkable cohort of students from all the over the world for our hands-on course on human brain #assembloids and #organoids! Amazing energy as they learn methods and approaches developed in the lab over the years, and as we discuss and troubleshoot the projects they are building back home. I am incredibly grateful to my entire lab for teaching this course with such dedication every year, and especially to the 3 superstars directing it: Merve Avar & Sabina Kanton & Rebecca Levy! This free-of-charge, annual course organized by our Stanford @BrOrganogenesis Center has helped hundreds of laboratories around the world adopt human stem cell models to study evolution, development, and disease.

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. In this new @biorxivpreprint, 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. The resulting neuromodulatory #assemboids allowed us to monitor serotonin release using genetically encoded serotonin 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. More needs to be done, but this is a first step toward understanding how neuromodulation shapes aspects of human development and disease. This work was led by a incredible group of scientists in lab: Sabina Kanton, Xiangling Meng, Chunyang Dong, Fikri Birey. Video below depicts responses to serotonin of neurons in human cortical organoids captured with the PsychLight2 sensor.

This week, we report in @Nature our effort to identify molecular convergence and divergence in #autism spectrum disorder (ASD) using human stem cell models. In this collaborative study with Dan Geschwind's lab, spanning almost a decade, we derived 96 hiPS cell lines representing 8 genetic forms of ASD, idiopathic patients, and 20 controls, and after rigorous quality control differentiated 70 lines in more than 150 experiments into human cortical #organoids for 100 days. Interestingly, early time points harbored the largest mutation-specific changes, but distinct mutations converged on shared transcriptional changes as development progressed. This is just the beginning: we will need larger cohorts and more advanced cultures that capture cell diversity and interactions, such as #assembloids. 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 work was spearheaded by the heroic efforts of Aaron Gordon and Se-Jin Yoon, together with Lucy Bicks!

By popular demand — the next edition of our hands-on @Stanford @BrOrganogenesis course is coming in 2026! This year, the focus turns to neural #assembloids, reflecting the growing movement toward modeling circuit-level and complex cell-cell interactions in brain disease. The course remains free (including lodging) and is taught by my lab for a full week. We look forward to welcoming another cohort of 20 participants from all over the world selected from hundreds of applications each year. Organized by an amazing trio of scientists: @RebeccaJLevyMD, Sabina Kanton, and Merve Avar. Supported by @BrOrganogenesis, @StanfordBrain, @StanfordBioX, and @NIH_NINDS. 🧠 Deadline: mid-December

Our latest work is out today in @ScienceMagazine: a self-organizing system that models organizer-driven patterning and commissural axon guidance in human neural development. This was achieved with human midline #assembloids by combining floor plate and spinal cord #organoids from pluripotent stem cells. A key advance is the three-part configuration (a floor plate squeezed in between two spinal cords), which enables human axons to cross the midline (and the subsequent synchronization of activity between the two parts seen in the video below). This platform opens the door to many applications; here, we used it to screen and identify human-enriched midline crossing regulators. Work led by @massimo_onesto with Neal Amin

Today in @Nature, we report human sensory #assembloids—the most complex 3D assembloids to date—comprising four integrated parts to recapitulate aspects of the spinothalamic pathway that processes pain stimuli. We use this model to investigate cellular/early circuit level features of genetic pain syndromes. More details to follow. Work pioneered in the lab by the brilliant Ji-il Kim and Kent Imaizumi, and in close collaboration with @GregScherrer25! Link below 👇

As stem cell-based modeling of the human nervous system and disease advances, we recently shared a group-effort framework in @Nature on designing experiments with #organoids, #assembloids, and transplantation Here a few key takeaways in 6 slides👇

In this week’s @Nature, we publish a group effort to outline a framework for studies with neural #organoids, #assembloids and transplantation. More details below 1/n

Glad to announce a new edition of our popular, free, hands-on @Stanford course on making, probing and manipulating neural #assembloids and #organoids Organized by an amazing trio in the lab: @RebeccaJLevyMD @FreddyMValencia and Merve Avar Deadline in mid-December Supported by the @BrOrganogenesis and @StanfordBrain @StanfordBioX and @NIH_NINDS

Today we introduce human neural loop #assembloids created from 4 parts derived from stem cells to study the cortico-striato-midbrain-thalamo-cortical pathway and to model neurodevelopmental disease Work led by the remarkable Ji-Il Kim and Yuki Miura in the lab. Also in collaboration with the @marius10p lab at @HHMIJanelia Video shows a four-part neural assembloid displaying emergent synchronized activity after a couple of hundred days of integration