A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Nature, Год журнала: 2023, Номер 624(7991), С. 317 - 332

Опубликована: Дек. 13, 2023

The mammalian brain consists of millions to billions cells that are organized into many cell types with specific spatial distribution patterns and structural functional properties1-3. Here we report a comprehensive high-resolution transcriptomic cell-type atlas for the whole adult mouse brain. was created by combining single-cell RNA-sequencing (scRNA-seq) dataset around 7 million profiled (approximately 4.0 passing quality control), approximately 4.3 using multiplexed error-robust fluorescence in situ hybridization (MERFISH). is hierarchically 4 nested levels classification: 34 classes, 338 subclasses, 1,201 supertypes 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, visualize whole-brain along MERFISH datasets. systematically analysed neuronal non-neuronal across identified high degree correspondence between identity specificity each type. results reveal unique features organization different regions-in particular, dichotomy dorsal ventral parts part contains relatively fewer yet highly divergent types, whereas more numerous closely related other. Our study also uncovered extraordinary diversity heterogeneity neurotransmitter neuropeptide expression co-expression types. Finally, found transcription factors major determinants classification combinatorial factor code defines all establishes benchmark reference foundational resource integrative investigations cellular circuit function, development evolution

Язык: Английский

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Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Янв. 18, 2023

Spatially resolved transcriptomics involves a set of emerging technologies that enable the transcriptomic profiling tissues with physical location expressions. Although variety methods have been developed for data integration, most them are single-cell RNA-seq datasets without consideration spatial information. Thus, can integrate from multiple tissue slides, possibly individuals, needed. Here, we present PRECAST, integration method complex batch effects and/or biological between slides. PRECAST unifies factor analysis simultaneously clustering and embedding alignment, while requiring only partially shared cell/domain clusters across datasets. Using both simulated four real datasets, show improved detection outstanding visualization, estimated aligned embeddings labels facilitate many downstream analyses. We demonstrate is computationally scalable applicable to different platforms.

Язык: Английский

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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 6, 2023

The mammalian brain is composed of millions to billions cells that are organized into numerous cell types with specific spatial distribution patterns and structural functional properties. An essential step towards understanding function obtain a parts list, i.e., catalog types, the brain. Here, we report comprehensive high-resolution transcriptomic type atlas for whole adult mouse was created based on combination two single-cell-level, whole-brain-scale datasets: single-cell RNA-sequencing (scRNA-seq) dataset ~7 million profiled, spatially resolved ~4.3 using MERFISH. hierarchically five nested levels classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes 5,200 clusters. We systematically analyzed neuronal, non-neuronal, immature neuronal across identified high degree correspondence between identity specificity each type. results reveal unique features organization in different regions, particular, dichotomy dorsal ventral brain: part contains relatively fewer yet highly divergent whereas more closely related other. also characterized cell-type expression neurotransmitters, neuropeptides, transcription factors. study uncovered extraordinary diversity heterogeneity neurotransmitter neuropeptide co-expression brain, suggesting they mediate myriad modes intercellular communications. Finally, found factors major determinants classification combinatorial factor code defines all whole-mouse-brain establishes benchmark reference foundational resource deep integrative investigations circuit function, development, evolution

Язык: Английский

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Olfactory testing in infants with perinatal asphyxia: enhancing encephalopathy risk stratification for future health outcomes

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер unknown, С. 106029 - 106029

Опубликована: Янв. 1, 2025

Язык: Английский

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A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains

Nature Genetics, Год журнала: 2023, Номер 55(12), С. 2104 - 2116

Опубликована: Ноя. 30, 2023

Abstract Conventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular mammalian brain. Profiling approximately 1.5 million transcriptomes 400,000 chromatin accessibility profiles across diverse mouse brains, identified over 300 subtypes, uncovering their molecular characteristics spatial locations. This comprehensive view elucidates expanded or depleted upon aging. We also investigated cell-type-specific responses genetic alterations linked Alzheimer’s disease, identifying associated types. Additionally, by profiling 118,240 human brain transcriptomes, discerned cell- region-specific transcriptomic changes tied pathogenesis. In conclusion, this research offers a valuable resource probing both normal pathological

Язык: Английский

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Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers

Science, Год журнала: 2023, Номер 382(6673), С. 958 - 963

Опубликована: Ноя. 23, 2023

Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in niche, give rise different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains usually quiescent, recruited gestation days during pregnancy. Synchronized activation these NSC pools generates transient waves short-lived OB interneurons, especially layers with less neurogenesis under homeostasis. Using spatial transcriptomics, identified molecular markers pregnancy-associated interneurons and showed some subsets temporarily needed for own pup recognition. Thus, pregnancy triggers yet behaviorally relevant neurogenesis, highlighting physiological relevance cell heterogeneity.

Язык: Английский

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Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes

Frontiers in Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Апрель 25, 2022

Forebrain development in vertebrates is regulated by transcription factors encoded homeobox, bHLH and forkhead gene families throughout the progressive overlapping stages of neural induction patterning, regional specification generation neurons glia from central nervous system (CNS) progenitor cells. Moreover, cell fate decisions, differentiation migration these committed CNS progenitors are controlled regulatory networks that various homeodomain-containing factors, including but not limited to those

Язык: Английский

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Illuminating the terminal nerve: Uncovering the link between GnRH‐1 neuron and olfactory development

The Journal of Comparative Neurology, Год журнала: 2024, Номер 532(3)

Опубликована: Март 1, 2024

Abstract During embryonic development, the olfactory placode (OP) generates migratory neurons, including pioneer cells of terminal nerve (TN), gonadotropin‐releasing hormone‐1 (GnRH‐1) and other uncharacterized neurons. Pioneer neurons from OP induce bulb (OB) morphogenesis. In mice, GnRH‐1 appear in system around mid‐gestation migrate via TN axons to different brain regions. The are crucial controlling hypothalamic‐pituitary‐gonadal axis. Kallmann syndrome is characterized by impaired defective OBs, secretion GnRH‐1, infertility. precise mechanistic link between development remains unclear. Studies humans mice highlight importance prokineticin‐2/prokineticin‐receptor‐2 (Prokr2) signaling pathway OB morphogenesis neuronal migration. Prokr2 loss‐of‐function mutations can cause (KS), hence represents a unique model decipher olfactory/GnRH‐1 connection. We discovered that expressed during critical period neuron formation, migration, induction Single‐cell RNA sequencing identified formed distinct express multiple genes associated with KS. Our study suggests aberrant pioneer/TN might KS spectrum.

Язык: Английский

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The Olfactory Bulb in Companion Animals—Anatomy, Physiology, and Clinical Importance

Brain Sciences, Год журнала: 2023, Номер 13(5), С. 713 - 713

Опубликована: Апрель 24, 2023

The Olfactory Bulb is a component of the System, in which it plays an essential role as interface between peripheral components and cerebral cortex responsible for olfactory interpretation discrimination. It this element that first selective integration stimuli occurs through complex cell interaction forwards received information to higher cortical centers. Considering its position organizational hierarchy system, now known changes can lead abnormalities. Through imaging techniques, was possible establish relationships occurrence secondary brain aging senility, neurodegenerative diseases, head trauma, infectious diseases with decrease size acuity. In companion animals, relationship has also been identified, observations relations cranial conformation, disposition, size, shape Bulb, structural alterations associated different etiologies. However, greater difficulty quantitatively assessing acuity animals manifestly smaller number studies dedicated topic maintain lack concrete unequivocal results field veterinary sciences. aim work revisit all dimensions, review anatomy histological characteristics, physiological importance potential early indicator establishment specific pathologies, well techniques evaluation vivo clinical exploration.

Язык: Английский

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The neurobiological effects of senescence on dopaminergic system: A comprehensive review

Journal of Chemical Neuroanatomy, Год журнала: 2024, Номер 137, С. 102415 - 102415

Опубликована: Март 22, 2024

Язык: Английский

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