Molecular and cellular dynamics of the developing human neocortex

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation1. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 neocortical samples encompassing both prefrontal cortex primary visual cortex. These span five main developmental stages, ranging first trimester to adolescence. In parallel, performed spatial transcriptomic analysis on a subset illustrate organization intercellular communication. This atlas enables us catalogue cell-type-specific, age-specific area-specific regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification lineage-tracing experiments, have untangled lineage relationships among subtypes during neurogenesis-to-gliogenesis transition. We identified tripotential intermediate subtype—tripotential cells (Tri-IPCs)—that responsible for local production GABAergic neurons, oligodendrocyte precursor astrocytes. Notably, most glioblastoma resemble Tri-IPCs at level, suggesting that cancer hijack processes enhance growth heterogeneity. Furthermore, integrating our with large-scale genome-wide association study data, created disease-risk map highlighting enriched risk associated autism spectrum disorder in second-trimester intratelencephalic neurons. Our sheds light molecular dynamics developing neocortex. Tripotential are astrocytes

Язык: Английский

---

Evolutionary convergence of sensory circuits in the pallium of amniotes

Science, Год журнала: 2025, Номер 387(6735)

Опубликована: Янв. 2, 2025

The amniote pallium contains sensory circuits that are structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. We used birthdating analysis, single-cell RNA spatial transcriptomics, mathematical modeling to compare the development evolution of known pallial across birds (chick), lizards (gecko), mammals (mouse). reveal neurons within these circuits’ stations generated at varying developmental times brain regions species found an early divergence in transcriptomic progression glutamatergic neurons. Our research highlights distinctions functional similarities circuit between mammals, suggesting convergence high-order processing lineages.

Язык: Английский

---

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Frontiers in Cellular Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Сен. 10, 2020

Research on critical periods of brain development is greatly expanding our understanding the cellular and molecular mechanisms underlying epochs heightened plasticity driven by environmental influence. Novel studies have started to reveal that timely interventions during hold potential reorient abnormal developmental trajectories in animal models neurological neuropsychiatric disorders. In this review, we re-examine fundamental criteria characterize a period, highlighting recently discovered health disease. addition, touch upon technological improvements modelling human-derived neural networks vitro. These scientific advances associated with use manipulations immature represent promising new preclinical setting will allow future translatability into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum schizophrenia.

Язык: Английский

---

Mapping the molecular and cellular complexity of cortical malformations

Science, Год журнала: 2021, Номер 371(6527)

Опубликована: Янв. 21, 2021

The cerebral cortex is an intricate structure that controls human features such as language and cognition. Cortical functions rely on specialized neurons emerge during development from complex molecular cellular interactions. Neurodevelopmental disorders occur when one or several of these steps incorrectly executed. Although a number causal genes disease phenotypes have been identified, the sequence events linking disruption to clinical expression mostly remains obscure. Here, focusing malformations cortical development, we illustrate how interactions at genetic, cellular, circuit levels together contribute diversity variability in phenotypes. Using specific examples online resource, propose multilevel assessment processes key identifying points vulnerability developing new therapeutic strategies.

Язык: Английский

---

Advancing models of neural development with biomaterials

Nature reviews. Neuroscience, Год журнала: 2021, Номер 22(10), С. 593 - 615

Опубликована: Авг. 10, 2021

Язык: Английский

---