Molecular logic of cellular diversification in the mouse cerebral cortex

Bella, Daniela Di; Habibi, Ehsan; Stickels, Robert R.; Scalia, Gabriele; Brown, Juliana; Yadollahpour, Payman; Yang, Sung Min; Abbate, Catherine; Biancalani, Tommasso; Macosko, Evan Z.; Chen, Fei; Regev, Aviv; Arlotta, Paola

doi:10.1038/s41586-021-03670-5

Cited by 289 publications

(334 citation statements)

References 49 publications

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“…No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 3,4,8,15,34 .…”

Section: Sample Sizesmentioning

confidence: 68%

“…Three-dimensional genome architecture and DNA methylation represent two epigenome layers that are important for gene regulation, but have not yet been coupled to single-cell transcriptomic and accessibility measurements 3,4 . Our immunoFACS approach allowed us to combine the resolution and depth of bulk Hi-C/DNA methylation with cell-type specificity.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, profiling the transcriptional and chromatin accessibility landscape at single-cell resolution has improved our understanding of the temporal logic of lineage specification in the mouse 3 and human 4,5 developing cerebral cortex. However, studies that comprehensively assess the effect of multiple regulatory modalities on transcription remain scarce [6][7][8][9] .…”

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confidence: 99%

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Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler

et al. 2022

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How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression and chromatin accessibility in single cells and integrated these data with measurements of enhancer activity, DNA methylation and three-dimensional genome architecture in purified cell populations. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex.

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“…No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 3,4,8,15,34 .…”

Section: Sample Sizesmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler

et al. 2022

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“…To fully discern whether single progenitors allow for a fluid differentiation and maturation into different IN subtypes, single-cell spatial transcriptomics should be used [117,118]. This will enable a time-dependent analysis of single-cell specification from the same cell.…”

Section: Interneuron Diversity From Specific Versus Cardinal Progenitorsmentioning

confidence: 99%

Development, Diversity, and Death of MGE-Derived Cortical Interneurons

Williams

Riedemann

2021

IJMS

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In the mammalian brain, cortical interneurons (INs) are a highly diverse group of cells. A key neurophysiological question concerns how each class of INs contributes to cortical circuit function and whether specific roles can be attributed to a selective cell type. To address this question, researchers are integrating knowledge derived from transcriptomic, histological, electrophysiological, developmental, and functional experiments to extensively characterise the different classes of INs. Our hope is that such knowledge permits the selective targeting of cell types for therapeutic endeavours. This review will focus on two of the main types of INs, namely the parvalbumin (PV+) or somatostatin (SOM+)-containing cells, and summarise the research to date on these classes.

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“…Single-cell molecular profiling at developmental and adult stages further provide valuable insights into the mechanism of cell type diversification and cell fate decision , as well as the aberrant change of cell populations and gene regulatory network in diseases [20][21][22][23][24] . Moreover, recent state of art development of single-cell multimodal technology integrates gene expression analysis with epitranscriptomes, chromatin accessibilities, proteomes or spatial analysis, which would empower the pursuit for greater understanding to the biology field 25 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates

Liau

Jin

Chen

et al. 2021

Preprint

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Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.

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Molecular logic of cellular diversification in the mouse cerebral cortex

Cited by 289 publications

References 49 publications

Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler

Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler

Development, Diversity, and Death of MGE-Derived Cortical Interneurons

Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates

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