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Record W4407265858 · doi:10.1101/2025.02.07.637106

Early cell cycle genes in cortical organoid progenitors predict interindividual variability in infant brain growth trajectories

2025· preprint· en· W4407265858 on OpenAlexaff
Madison R. Glass, Nana Matoba, Alvaro A. Beltran, Niyanta K Patel, Tala M. Farah, K. Kedar Eswar, Karen Huang, Ian Curtin, Sara M. Ahmed, Mary Srivastava, Emma Drake, Liam T. Davis, Meghana Yeturi, Kexin Sun, Michael I. Love, Jeremy M. Simon, Tanya St. John, Natasha Marrus, Juhi Pandey, Annette Estes, Stephen R. Dager, Robert T. Schultz, Kelly N. Botteron, Alan C. Evans, Sun Hyung Kim, Martin Styner, Robert C. McKinstry, D. Louis Collins, Heather E. Volk, Kelly S. Benke, Lonnie Zwaigenbaum, Heather C. Hazlett, Adriana S. Beltrán, Jessica B. Girault, Mark D. Shen, Joseph Piven, Jason L. Stein

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsMcGill UniversityUniversity of AlbertaMcGill University Health Centre
FundersNational Institute of Neurological Disorders and StrokeIntellectual and Developmental Disabilities Research CenterSchool of Medicine, University of North Carolina at Chapel HillNational Institutes of HealthFoundation of Hope for Research and Treatment of Mental IllnessLineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillNorth Carolina Biotechnology Center
KeywordsOrganoidBiologyNeuroscienceProgenitorProgenitor cellBrain developmentInfant developmentHuman brainStem cellPsychologyCell biologyDevelopmental psychology

Abstract

fetched live from OpenAlex

Summary Human induced pluripotent stem cell (iPSC) derived cortical organoids (hCOs) model neurogenesis on an individual’s genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from which they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who have undergone longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of cortical hem cells were associated with in vivo cortical growth rates. Cell cycle associated genes expression in early progenitors at the crux of fate decision trajectories were correlated with cortical growth rate from 6-12 months of age, and were enriched in microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types influencing infant cortical surface area expansion.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.007
GPT teacher head0.227
Teacher spread0.220 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2025
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicPluripotent Stem Cells ResearchFrench-language works237,207