Precision and Accuracy of Single-Cell/Nuclei RNA Sequencing Data DOI Creative Commons
Rujia Dai, Ming Zhang, Tianyao Chu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 15, 2024

Abstract Single-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue the quality of sc/snRNA-Seq data that would impact reliability downstream analyses. Here we evaluated precision and accuracy 18 datasets. The was assessed on from human brain studies with a total 3,483,905 cells 297 individuals, by utilizing technical replicates. sample-matched scRNA-Seq pooled-cell RNA-Seq cultured mononuclear phagocytes four species. results revealed low at single-cell level across all data. Cell number were highlighted as two key factors determining expression precision, accuracy, reproducibility differential analysis sc/snRNA-Seq. This study underscores necessity enough high-quality per cell type individual, preferably hundreds, to mitigate noise quantification.

Язык: Английский

Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex DOI
Daniela J. Di Bella, Nuria Domıńguez-Iturza, Juliana Brown

и другие.

Neuron, Год журнала: 2024, Номер 112(13), С. 2091 - 2111

Опубликована: Май 15, 2024

Язык: Английский

Процитировано

19
Molecular and cellular dynamics of the developing human neocortex DOI Creative Commons
Li Wang, Cheng Wang, Juan Moriano

и другие.

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

Процитировано

10
Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex DOI Creative Commons
Martin Munz, Arjun Bharioke, Georg Kosche

и другие.

Cell, Год журнала: 2023, Номер 186(9), С. 1930 - 1949.e31

Опубликована: Апрель 1, 2023

Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that mouse Rbp4-Cre cortical neurons, transcriptomically closest to layer 5 pyramidal display two phases circuit in vivo. At E14.5, they form a multi-layered motif, only near-projecting-type neurons. By E17.5, this transitions second motif involving all three types, analogous the adult types. In vivo patch clamp recordings and two-photon calcium imaging neurons reveal active somas neurites, tetrodotoxin-sensitive voltage-gated conductances, functional glutamatergic synapses, from E14.5 onwards. Embryonic strongly express autism-associated genes perturbing these interferes with switch between motifs. Hence, active, transient, at inception neocortex, studying could yield insights into etiology autism.

Язык: Английский

Процитировано

27
Microglial contribution to the pathology of neurodevelopmental disorders in humans DOI Creative Commons
Rugilė Matulevičiūtė,

Elizabeth Toyin Akinluyi,

Tim A.O. Muntslag

и другие.

Acta Neuropathologica, Год журнала: 2023, Номер 146(5), С. 663 - 683

Опубликована: Сен. 1, 2023

Abstract Microglia are the brain’s resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter telencephalic wall by 4th postconceptional week colonise fetal in a manner that spatiotemporally tracks key neurodevelopmental humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human warranting further focus on condition, particularly as emerging critically involved pathological signature cognitive disorders. In this article, review evidence supporting microglial involvement basic focusing species. We next concur neuropathological demonstrating whether contribute to aetiology two disorders: autism spectrum conditions schizophrenia. Next, highlight recent technologies have revolutionised our understanding biology with these tools can help us elucidate at unprecedented resolution links conclude reviewing current treatment approaches shown most promise towards targeting disorders suggest novel avenues future consideration.

Язык: Английский

Процитировано

24
Cell-type-specific effects of age and sex on human cortical neurons DOI Creative Commons
Jo-fan Chien, Hanqing Liu, Bang-An Wang

и другие.

Neuron, Год журнала: 2024, Номер 112(15), С. 2524 - 2539.e5

Опубликована: Июнь 5, 2024

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation transcriptome sequencing (snmCT-seq) in frontal cortex from young adult aged donors, we found widespread age- sex-related variation specific neuron types. The proportion inhibitory SST- VIP-expressing neurons was reduced donors. Excitatory had more profound age-related their gene expression than cells. Hundreds genes involved synaptic activity, including EGR1, were less expressed adults. Genes located subtelomeric regions increased age correlated telomere length. We further mapped cell-type-specific sex differences X-inactivation escape genes. Multi-omic epigenomes transcriptomes provide new insight into the effects on human neurons.

Язык: Английский

Процитировано

17
Molecular and cellular dynamics of the developing human neocortex at single-cell resolution DOI Creative Commons
Li Wang, Cheng Wang, Juan Moriano

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 16, 2024

The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility 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 subset illustrate organization intercellular communication. This atlas enables us catalog cell type-, age-, area-specific regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification, lineage-tracing experiments, have untangled lineage relationships among subtypes during transition neurogenesis gliogenesis in neocortex. We identified tripotential intermediate subtype, termed Tri-IPC, responsible for local production GABAergic neurons, oligodendrocyte precursor cells, astrocytes. Remarkably, most glioblastoma cells resemble Tri-IPCs at level, suggesting that cancer hijack processes enhance growth heterogeneity. Furthermore, integrating our with large-scale GWAS data, created disease-risk map highlighting enriched ASD risk second-trimester intratelencephalic projection neurons. Our study sheds light landscape dynamics developing

Язык: Английский

Процитировано

13
Developmental origin of oligodendrocytes determines their function in the adult brain DOI Creative Commons

Sarah Foerster,

Elisa M. Floriddia, David van Bruggen

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(8), С. 1545 - 1554

Опубликована: Июнь 7, 2024

In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three regions in a spatiotemporal gradient ventral to dorsal. However, functional importance of this developmental heterogeneity is unknown. Using genetic strategy ablate dorsally derived lineage cells (OLCs), we show here that areas which OLCs normally reside adult central nervous system become populated myelinated by origin. These ectopic oligodendrocytes (eOLs) have distinctive gene expression profile as well subtle myelination abnormalities. The failure eOLs fully assume role original results locomotor cognitive deficits animal. This study reveals within its for homeostatic brain function.

Язык: Английский

Процитировано

12
Modelling human brain development and disease with organoids DOI
Marcella Birtele, Madeline A. Lancaster, Giorgia Quadrato

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Язык: Английский

Процитировано

11
Standardizing designed and emergent quantitative features in microphysiological systems DOI
Dennis M. Nahon, Renée Moerkens,

Hande Aydoğmuş

и другие.

Nature Biomedical Engineering, Год журнала: 2024, Номер 8(8), С. 941 - 962

Опубликована: Авг. 26, 2024

Язык: Английский

Процитировано

10
Organizational Principles of the Primate Cerebral Cortex at the Single‐Cell Level DOI Creative Commons
Renrui Chen, Pengxing Nie, Liangxiao Ma

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract The primate cerebral cortex, the major organ for cognition, consists of an immense number neurons. However, organizational principles governing these neurons remain unclear. By accessing single‐cell spatial transcriptome over 25 million neuron cells across entire macaque it is discovered that distribution within cortical layers highly non‐random. Strikingly, three‐quarters are located in distinct neuronal clusters. Within clusters, different cell types tend to collaborate rather than function independently. Typically, excitatory clusters mainly consist excitatory‐excitatory combinations, while inhibitory primarily contain excitatory‐inhibitory combinations. Both cluster have roughly equal numbers each layer. Importantly, most and form partnerships, indicating a balanced local network correlating with specific functional regions. These conserved mouse findings suggest brain regions cortex may exhibit similar mechanisms at population level.

Язык: Английский

Процитировано

1