Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution

Trevino, Alexandro E.; Müller, Fabian; Andersen, Jimena; Sundaram, Laksshman; Kathiria, Arwa S.; Shcherbina, Anna; Farh, Kyle Kai‐How; Chang, Howard Y.; Pașca, Anca M.; Kundaje, Anshul; Paşca, Sergiu P.; Greenleaf, William J.

doi:10.1016/j.cell.2021.07.039

Cited by 246 publications

(334 citation statements)

References 70 publications

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“…Considering that the majority of transcription factors occur in SOM + INs [71], it is postulated that PV + cell identity represents the 'default state' of MGE-derived INs and only the active suppression of this state, by induction of select transcription factors, permits a SOM + IN phenotype. The difficulty in simulating the expression of time, location, and tissuedependent transcription factors in vitro is highlighted by only partial establishment of in vivo PV:SOM IN ratios from mouse embryonic stem cell-derived interneurons when transplanted into the somatosensory cortex [114][115][116].…”

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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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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“…Although limited availability of developing human telencephalon tissue restricts research efforts, recent studies have shown that the chromatin structure changes during telencephalic development. [77][78][79][80][81][82][83] Among these studies, those focusing on chromatin accessibility have revealed the differences in chromatin structure between different regions of the developing telencephalon.…”

Section: Chromatin Accessibility Is Associated With Human Telencephalon Regionalizationmentioning

confidence: 99%

Brain regionalization by Polycomb‐group proteins and chromatin accessibility

Eto

Kishi

2021

BioEssays

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During brain development, neural precursor cells (NPCs) in different brain regions produce different types of neurons, and each of these regions plays a different role in the adult brain. Therefore, precise regionalization is essential in the early stages of brain development, and irregular regionalization has been proposed as the cause of neurodevelopmental disorders. The mechanisms underlying brain regionalization have been well studied in terms of morphogen-induced expression of critical transcription factors for regionalization. NPC potential in different brain regions is defined by chromatin structures that regulate the plasticity of gene expression. Herein, we present recent findings on the importance of chromatin structure in brain regionalization, particularly with respect to its regulation by Polycomb-group proteins and chromatin accessibility.

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“…Although not directly coding for a specific gene, the non-coding portion of the genome has a very important role in regulating the where, how, and what is expressed in a type of tissue, such as the brain, at any given moment [ 25 , 26 , 27 , 28 ]. Indeed, around 98% of the genome is composed of non-coding elements, with more than 30% of it having a regulatory function [ 29 ].…”

Section: Ngs Impact On Ndd Diagnosismentioning

confidence: 99%

“…Indeed the consequences of mutations can vary depending on the cell type, as seen in Parkinson’s and Alzheimer’s disease [ 49 ]. Recently, this has also been proven in human cortical development [ 27 ]. Thanks to the use of a neural network approach (BPNet, [ 50 ]), the authors were able to describe the effect of mutations in a specific cell type using a large single-cell dataset coupled with the Simons Simplex Collection catalog, which comprises over 200,000 pathological variants.…”

Section: Ngs Impact On Ndd Diagnosismentioning

confidence: 99%

“…The integration of multiple single cell approaches has been recently used to reveal new insights into the human cortical development by directly applying it to primary human embryonic brain tissue [ 27 ]. Here, a huge ATLAS of single cells transcriptomes (57,868) and epigenomes (31,304) spanning four different gestational times were generated.…”

Section: Ngs In Experimental Modelling Of Nddsmentioning

confidence: 99%

See 1 more Smart Citation

Rare Does Not Mean Worthless: How Rare Diseases Have Shaped Neurodevelopment Research in the NGS Era

et al. 2021

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The advent of next-generation sequencing (NGS) is heavily changing both the diagnosis of human conditions and basic biological research. It is now possible to dig deep inside the genome of hundreds of thousands or even millions of people and find both common and rare genomic variants and to perform detailed phenotypic characterizations of both physiological organs and experimental models. Recent years have seen the introduction of multiple techniques using NGS to profile transcription, DNA and chromatin modifications, protein binding, etc., that are now allowing us to profile cells in bulk or even at a single-cell level. Although rare and ultra-rare diseases only affect a few people, each of these diseases represent scholarly cases from which a great deal can be learned about the pathological and physiological function of genes, pathways, and mechanisms. Therefore, for rare diseases, state-of-the-art investigations using NGS have double valence: their genomic cause (new variants) and the characterize the underlining the mechanisms associated with them (discovery of gene function) can be found. In a non-exhaustive manner, this review will outline the main usage of NGS-based techniques for the diagnosis and characterization of neurodevelopmental disorders (NDDs), under whose umbrella many rare and ultra-rare diseases fall.

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Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution

Cited by 246 publications

References 70 publications

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

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

Brain regionalization by Polycomb‐group proteins and chromatin accessibility

Rare Does Not Mean Worthless: How Rare Diseases Have Shaped Neurodevelopment Research in the NGS Era

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