A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.
Zizhen YaoCindy T J van VelthovenMichael KunstMeng ZhangDelissa A McMillenChangkyu LeeWon JungJeff GoldyAliya AbdelhakPamela BakerEliza R BarkanDarren BertagnolliJazmin CamposDaniel CareyTamara CasperAnish Bhaswanth ChakkaRushil ChakrabartySakshi ChavanMin ChenMichael ClarkJennie CloseKirsten CrichtonScott DanielTim DolbeareLauren EllingwoodJames C GeeAlexandra GlandonJessica GloeJoshua GouldJames GrayNathan GuilfordJunitta B GuzmanDaniel HirschsteinWindy HoKelly JinMatthew KrollKanan LathiaArielle LeonBrian R LongZoe MaltzerNaomi X MartinRachel McCueEmma MeyerdierksThuc Nghi NguyenTrangthanh H PhamChristine RimorinAugustin RuizNadiya ShapovalovaClifford R SlaughterbeckJosef SulcMichael TieuAmy TorkelsonHerman TungNasmil Valera CuevasKatherine WadhwaniKatelyn KiickBoaz P LeviColin FarrellCarol L ThompsonShoaib MuftiChelsea M PaganLauren KruseNick DeeSusan M SunkinChristina KouskoutiMichael J HawrylyczJack WatersLydia NgKimberly A SmithBosiljka TasicXiaowei ZhuangHongkui ZengPublished in: bioRxiv : the preprint server for biology (2023)
The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single- cell RNA-sequencing (scRNA-seq) dataset of ∼7 million cells profiled, and a spatially resolved transcriptomic dataset of ∼4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.
Keyphrases
- single cell
- rna seq
- resting state
- cerebral ischemia
- high throughput
- white matter
- transcription factor
- functional connectivity
- high resolution
- poor prognosis
- machine learning
- induced apoptosis
- spinal cord
- cell therapy
- brain injury
- deep learning
- spinal cord injury
- deep brain stimulation
- young adults
- childhood cancer
- liquid chromatography
- long non coding rna