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

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 317 - 332

Published: Dec. 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

Language: Английский

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What is a cell type and how to define it?

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

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Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish

Frontiers in Science, Journal Year: 2023, Volume and Issue: 1

Published: Feb. 28, 2023

Recent advances in human stem cell-derived brain organoids promise to replicate critical molecular and cellular aspects of learning memory possibly cognition vitro . Coining the term “organoid intelligence” (OI) encompass these developments, we present a collaborative program implement vision multidisciplinary field OI. This aims establish OI as form genuine biological computing that harnesses using scientific bioengineering an ethically responsible manner. Standardized, 3D, myelinated can now be produced with high cell density enriched levels glial cells gene expression for learning. Integrated microfluidic perfusion systems support scalable durable culturing, spatiotemporal chemical signaling. Novel 3D microelectrode arrays permit high-resolution electrophysiological signaling recording explore capacity recapitulate mechanisms formation and, ultimately, their computational potential. Technologies could enable novel biocomputing models via stimulus-response training organoid-computer interfaces are development. We envisage complex, networked whereby connected real-world sensors output devices, ultimately each other sensory organ (e.g. retinal organoids), trained biofeedback, big-data warehousing, machine methods. In parallel, emphasize embedded ethics approach analyze ethical raised by research iterative, manner involving all relevant stakeholders. The many possible applications this urge strategic development discipline. anticipate OI-based allow faster decision-making, continuous during tasks, greater energy data efficiency. Furthermore, “intelligence-in-a-dish” help elucidate pathophysiology devastating developmental degenerative diseases (such dementia), potentially aiding identification therapeutic approaches address major global unmet needs.

Language: Английский

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Single-cell and spatial transcriptomics: deciphering brain complexity in health and disease

Nature Reviews Neurology, Journal Year: 2023, Volume and Issue: 19(6), P. 346 - 362

Published: May 17, 2023

Language: Английский

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Neuronal wiring diagram of an adult brain

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 124 - 138

Published: Oct. 2, 2024

Language: Английский

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Large Language Models and the Reverse Turing Test

Neural Computation, Journal Year: 2023, Volume and Issue: 35(3), P. 309 - 342

Published: Feb. 6, 2023

Large language models (LLMs) have been transformative. They are pretrained foundational that self-supervised and can be adapted with fine-tuning to a wide range of natural tasks, each which previously would required separate network model. This is one step closer the extraordinary versatility human language. GPT-3 and, more recently, LaMDA, both them LLMs, carry on dialogs humans many topics after minimal priming few examples. However, there has reactions debate whether these LLMs understand what they saying or exhibit signs intelligence. high variance exhibited in three interviews reaching wildly different conclusions. A new possibility was uncovered could explain this divergence. What appears intelligence may fact mirror reflects interviewer, remarkable twist considered reverse Turing test. If so, then by studying interviews, we learning about beliefs interviewer than LLMs. As become capable, transform way interact machines how other. Increasingly, being coupled sensorimotor devices. talk talk, but walk walk? road map for achieving artificial general autonomy outlined seven major improvements inspired brain systems turn used uncover insights into function.

Language: Английский

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Cortical somatostatin interneuron subtypes form cell-type-specific circuits

Neuron, Journal Year: 2023, Volume and Issue: 111(17), P. 2675 - 2692.e9

Published: June 29, 2023

Language: Английский

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Genetics of human brain development

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: 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), Journal Year: 2023, Volume and Issue: unknown

Published: March 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

Language: Английский

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Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

Nature Nanotechnology, Journal Year: 2023, Volume and Issue: 18(10), P. 1241 - 1251

Published: July 10, 2023

Abstract Crossing the blood–brain barrier in primates is a major obstacle for gene delivery to brain. Adeno-associated viruses (AAVs) promise robust, non-invasive from bloodstream However, unlike rodents, few neurotropic AAVs efficiently cross non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening adult marmosets and newborn macaques, which has improved efficiency brains of multiple primate species: marmoset, rhesus macaque green monkey. CAP-Mac neuron biased infant Old World primates, exhibits broad tropism macaques vasculature marmosets. We demonstrate applications single, intravenous dose deliver functional GCaMP ex vivo calcium imaging across brain areas, or cocktail fluorescent reporters Brainbow-like labelling throughout brain, circumventing need germline manipulations As such, shown have potential systemic transfer

Language: Английский

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