Human Brain Ancestral Barcodes DOI Open Access
Darryl Shibata

Published: Dec. 27, 2024

Dynamic CpG methylation “barcodes” were read from 15,000 to 21,000 single cells three human male brains. To overcome sparse sequencing coverage, the barcode had ∼31,000 rapidly fluctuating X-chromosome sites (fCpGs), with at least 500 covered per cell and 30 common between pairs (average of ∼48). Barcodes appear start methylated record mitotic ages because excitatory neurons glial that emerge later in development less methylated. are different most cells, average pairwise differences (PWDs) ∼0.5 cells. About 10 million more closely related PWDs < 0.05. ancestry reconstruct trees where similar phenotypes, albeit some phenotypic differences. Inhibitory showed evidence tangential migration than neurons, cortical regions. fCpG barcodes become polymorphic during can distinguish thousands

Language: Английский

A molecular and cellular perspective on human brain evolution and tempo DOI
Feline W Lindhout, Fenna M. Krienen, Katherine S. Pollard

et al.

Nature, Journal Year: 2024, Volume and Issue: 630(8017), P. 596 - 608

Published: June 19, 2024

Language: Английский

Citations

18
NOTCH, ERK, and SHH signaling respectively control the fate determination of cortical glia and olfactory bulb interneurons DOI Creative Commons

Yanjing Gao,

Mengge Sun, Tao Fu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(9)

Published: Feb. 25, 2025

During cortical development, radial glial cells (neural stem cells) initially are neurogenic, generating intermediate progenitor that exclusively produce glutamatergic pyramidal neurons. Next, generate tripotential (Tri-IPCs) give rise to astrocytes and oligodendrocytes, olfactory bulb interneurons. The molecular mechanisms underlying the transition from neurogenesis gliogenesis, subsequent fate determination of astrocytes, interneurons, remain unclear. Here, we report extracellular signal-regulated kinase (ERK) signaling plays a fundamental role in promoting gliogenesis generation Tri-IPCs. Additionally, sonic hedgehog-smoothened-glioma-associated oncogene homolog (SHH-SMO-GLI) activator has an auxiliary function ERK during these processes. We further demonstrate that, Tri-IPCs, NOTCH is crucial for while prominent oligodendrocyte specification, SHH required provide evidence suggesting this mechanism conserved both mice humans. Finally, propose unifying principle mammalian gliogenesis.

Language: Английский

Citations

1
Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification DOI Creative Commons
Xuyu Qian, Kyle Coleman,

Shunzhou Jiang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens functionally specialized areas

Language: Английский

Citations

6
ARX regulates cortical interneuron differentiation and migration DOI Open Access
Youngshin Lim, Shyam K. Akula,

Abigail Myers

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Mutations in aristaless-related homeobox ( ARX ) are associated with neurodevelopmental disorders including developmental epilepsies, intellectual disabilities, and autism spectrum disorders, or without brain malformations. Aspects of these have been linked to abnormal cortical interneuron (cIN) development function. To further understand ARX's role cIN development, multiple Arx mutant mouse lines were interrogated. We found that is critical for controlling numbers distribution, especially, the developing marginal zone (MZ). Single cell transcriptomics ChIP-seq, combined functional studies, revealed directly indirectly regulates genes involved proliferation cycle (e.g., Bub3 , Cspr3 ), fate specification Nkx2.1 Maf Mef2c migration Lmo1 Cxcr4 Nrg1 ErbB4 ). Our data suggest MZ stream defects primarily result from disordered cell-cell communication. Together our findings provide new insights into mechanisms underlying how they disrupted several disorders.

Language: Английский

Citations

5
A comparative view of human and mouse telencephalon inhibitory neuron development DOI
Changuk Chung, Joseph G. Gleeson, Joseph G. Gleeson

et al.

Development, Journal Year: 2025, Volume and Issue: 152(1)

Published: Jan. 1, 2025

ABSTRACT Human GABAergic inhibitory neurons (INs) in the telencephalon play crucial roles modulating neural circuits, generating cortical oscillations, and maintaining balance between excitation inhibition. The major IN subtypes are based on their gene expression profiles, morphological diversity circuit-specific functions. Although previous foundational work has established that INs originate ganglionic eminence regions mice, recent studies have questioned origins humans non-human primates. We review of mice compare with findings from primary human prenatal brain tissue culture experiments lineage analysis somatic variants neurotypical cadavers organoids. Together, these suggest potential primate- or human-specific processes may been overlooked mouse models could implications for disorders.

Language: Английский

Citations

0
Somatic mosaicism and interneuron involvement in mTORopathies DOI

Lilian G Jerow,

Darcy A. Krueger, Christina Groß

et al.

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Comparative study of the effects of prenatal sevoflurane exposure at different cortical stages on forebrain development and maturation in offspring DOI Creative Commons
Tianyuan Wang,

Huandi Weng,

Yalan Li

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 3, 2025

Brain development involves several critical stages, such as proliferation, neuronal migration, axonal pathfinding, and connection formation. Sevoflurane, a γ-aminobutyric acid (GABA) receptor agonist, is widely used an inhaled general anesthetic. However, its impact on brain has raised increasing concerns, particularly regarding prenatal exposure. This study aims to investigate the effects of sevoflurane exposure (PSE) at different cortical focusing migration glutamatergic GABAergic neurons behavior in offspring. PSE was administered two stages: embryonic day (E) 12.5 E18.5. Double situ hybridization identify coexpression GABA receptors Pax6- Mash1-positive cells forebrain. The radial tangential were analyzed. Behavioral tests, including open-field test, elevated plus-maze forced swim tail suspension sucrose preference Morris water maze, performed offspring assess anxiety-like behaviors, depression, learning memory impairments. inhibits promotes neurons. Specifically, early (E12.5) inhibited expression Pax6-Tbr2-Tbr1 cascade Tbr1 ventral prefrontal cortex (PFC), whereas late (E18.5) this process dorsal side. In addition, mice with exhibited increased rather than demonstrated by reduced time spent center test open arms test. No significant differences observed or Furthermore, impairments maze. Our results indicate that E12.5 E18.5 leads abnormalities neurons, affecting long-term behaviors causing mice.

Language: Английский

Citations

0
Advances in single-cell DNA sequencing enable insights into human somatic mosaicism DOI
Diane D. Shao,

Andrea J. Kriz,

Daniel Snellings

et al.

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

Citations

0
Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia DOI Creative Commons
Sara Baldassari, Esther Klingler,

Lucia Gomez Teijeiro

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Focal cortical dysplasia type II (FCDII) is a malformation causing refractory epilepsy. FCDII arises from developmental somatic activating mutations in mTOR pathway genes, leading to focal dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic how they affect cell-type-specific transcriptional programs remain unknown. In the present study, we combined several single-nucleus genotyping transcriptomics approaches with spatial resolution surgical specimens patients genetically mosaic FCDII. Mutations were detected distinct types, including glutamatergic neurons astrocytes, small fraction of mutated cells exhibited features. Moreover, identified dysregulations both nonmutated cells, synapse- neurodevelopment-related pathways, that may account for epilepsy dysregulation mitochondrial metabolism pathways Together, these findings reveal cell-autonomous non-cell-autonomous features be leveraged precision medicine.

Language: Английский

Citations

0
The Principle of Cortical Development and Evolution DOI Creative Commons
Zhengang Yang

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Abstract Human’s robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes to the cerebral cortex. This paper reviews biology evolution of mammalian cortical radial glial cells (primary neural stem cells) introduces concept that a genetically step wise process, based on core molecular pathway already use, is process has molded neurogenesis. The mechanism, which been identified our recent studies, extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose basis for dwarfism, exemplified lissencephalic mouse originated from larger gyrencephalic ancestor, an increase SHH signaling glia, antagonizes ERK-BMP7 signaling. Finally, that: (1) not key regulator primate expansion folding; (2) human do generate neocortical interneurons; (3) human-specific genes may be essential most expansion. hope this review assists colleagues field, guiding research address gaps understanding development evolution.

Language: Английский

Citations

3