Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations
Bibliographic record
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder caused by genetic or environmental perturbations during early development. Diagnoses are dependent on the identification of behavioral abnormalities that likely emerge well after the disorder is established, leaving critical developmental windows uncharacterized. This is further complicated by the incredible clinical and genetic heterogeneity of the disorder that is not captured in most mammalian models. In recent years, advancements in stem cell technology have created the opportunity to model ASD in a human context through the use of pluripotent stem cells (hPSCs), which can be used to generate 2D cellular models as well as 3D unguided- and region-specific neural organoids. These models produce profoundly intricate systems, capable of modeling the developing brain spatiotemporally to reproduce key developmental milestones throughout early development. When complemented with multi-omics, genome editing, and electrophysiology analysis, they can be used as a powerful tool to profile the neurobiological mechanisms underlying this complex disorder. In this review, we will explore the recent advancements in hPSC-based modeling, discuss present and future applications of the model to ASD research, and finally consider the limitations and future directions within the field to make this system more robust and broadly applicable.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".