ArticleDevelopment (Cambridge, England)2024
A multi-layered integrative analysis reveals a cholesterol metabolic program in outer radial glia with implications for human brain evolution.
Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex.Science (New York, N.Y.) · 2026Article
- FABP7 controls radial glial scaffold stability during human cortical development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Zinc-Finger Protein POGZ Associates with Polycomb Repressive Complex 1 to Regulate Bone Morphogenetic Protein Signaling During Neuronal Differentiation.Stem cell reviews and reports · 2026Article
- Early developmental origins of cortical disorders modeled in human neural stem cells.Nature communications · 2025Article
- The cellular substrate of evolutionary novelty.Current biology : CB · 2025Review
- YY1 mutations disrupt corticogenesis through a cell-type specific rewiring of cell-autonomous and non-cell-autonomous transcriptional programs.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The definition of molecular and cellular mechanisms contributing to brain ontogenetic trajectories is essential to investigate the evolution of our species. Yet their functional dissection at an appropriate level of granularity remains challenging. Capitalizing on recent efforts that have extensively profiled neural stem cells from the developing human cortex, we develop an integrative computational framework to perform trajectory inference and gene regulatory network reconstruction, (pseudo)time-informed non-negative matrix factorization for learning the dynamics of gene expression programs, and paleogenomic analysis for a higher-resolution mapping of derived regulatory variants in our species in comparison with our closest relatives. We provide evidence for cell type-specific regulation of gene expression programs during indirect neurogenesis. In particular, our analysis uncovers a key role for a cholesterol program in outer radial glia, regulated by zinc-finger transcription factor KLF6. A cartography of the regulatory landscape impacted by Homo sapiens-derived variants reveals signals of selection clustering around regulatory regions associated with GLI3, a well-known regulator of radial glial cell cycle, and impacting KLF6 regulation. Our study contributes to the evidence of significant changes in metabolic pathways in recent human brain evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.