Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression

Amberg, Nicole; Pauler, Florian M.; Streicher, Carmen; Hippenmeyer, Simon

doi:10.1126/sciadv.abq1263

Cited by 8 publications

(2 citation statements)

References 77 publications

(157 reference statements)

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“…These results suggest a role for the polycomb complex and chromatin remodellers in the progression of the temporal programme in the neural tube (Fig 2F). This is consistent with the extension of the early temporal competence window in Drosophila neuroblasts lacking PRC1 or PRC2 (Lucas et al, 2021) although results in mammalian cortex (Amberg et al, 2022;Telley et al, 2019) highlights the complexity of regulating the temporal transitions.…”

Section: Resultssupporting

confidence: 83%

The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

Zhang,

Boezio,

Cornwall-Scoones

et al. 2024

Preprint

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The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organising cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here we define a global temporal programme in the spinal cord. This governs cell fate choices by regulating chromatin accessibility in neural progenitors. Perturbation of this cis-regulatory programme affects sequential transitions in spinal cord progenitors and the identity of progeny. The temporal programme operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin programme determines the output of a spatial gene regulatory network resulting in the temporally and spatially ordered allocation of cell type identity.

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Section: Resultssupporting

confidence: 83%

The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

Zhang,

Boezio,

Cornwall-Scoones

et al. 2024

Preprint

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“…Regulation via miRNAs [175, 176] and other RNA-mediated processes [177] may contribute to progenitor diversity. Dynamic changes in chromatin conformation could further diversify neural progenitor states [178‒181] and thus increase flexibility of neuronal differentiation. Some chromatin modifications may be transient, depending upon local interactions, cell cycle phases, and the abundance and activity in individual progenitors of proteins that regulate DNA methylation [182, 183] or histone modifications [171, 180].…”

Section: Lining Up For Altered States: Balancing Progenitor Identitie...mentioning

confidence: 99%

Out of Line or Altered States? Neural Progenitors as a Target in a Polygenic Neurodevelopmental Disorder

Rukh,

Meechan,

Maynard

et al. 2023

Dev Neurosci

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The genesis of a mature complement of neurons is thought to require, at least in part, precursor cell lineages in which neural progenitors have distinct identities recognized by exclusive expression of one or a few molecular markers. Nevertheless, limited progenitor types distinguished by specific markers and lineal progression through such subclasses cannot easily yield the magnitude of neuronal diversity in most regions of the nervous system. The late Verne Caviness, to whom this edition of Developmental Neuroscience is dedicated, recognized this mismatch. In his pioneering work on the histogenesis of the cerebral cortex, he acknowledged the additional flexibility required to generate multiple classes of cortical projection and interneurons. This flexibility may be accomplished by establishing cell states in which levels rather than binary expression or repression of individual genes vary across each progenitor’s shared transcriptome. Such states may reflect local, stochastic signaling via soluble factors or coincidence of cell surface ligand/receptor pairs in subsets of neighboring progenitors. This probabilistic, rather than determined, signaling could modify transcription levels via multiple pathways within an apparently uniform population of progenitors. Progenitor states, therefore, rather than lineal relationships between types may underlie the generation of neuronal diversity in most regions of the nervous system. Moreover, mechanisms that influence variation required for flexible progenitor states may be targets for pathological changes in a broad range of neurodevelopmental disorders, especially those with polygenic origins.

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Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression

Villalba,

Amberg,

Hippenmeyer

2023

Neocortical Neurogenesis in Development and Evolution

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Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression

Cited by 8 publications

References 77 publications

The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube

Out of Line or Altered States? Neural Progenitors as a Target in a Polygenic Neurodevelopmental Disorder

Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression

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