Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence

Yoon, Ki‐Jun; Vissers, Caroline; Ming, Guo Li; Song, Hongjun

doi:10.1083/jcb.201802117

Cited by 74 publications

(80 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transmission of temporal birthmarks from mother to daughter cell may occur via conserved local-or large-scale chromatin features, as suggested by the critical role of epigenetic regulation in temporal patterning identified here. In addition, the passive transmission of cytoplasmic RNA and posttranscriptional events may also be involved (17,(45)(46)(47)(48). This temporal birthmark fades with differentiation as environmental factors come into play.…”

Section: Discussionmentioning

confidence: 99%

Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Telley

Agirman

Prados

et al. 2019

Science

319

393

View full text Add to dashboard Cite

During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age–dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity.

show abstract

Section: Discussionmentioning

confidence: 99%

Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Telley

Agirman

Prados

et al. 2019

Science

319

393

View full text Add to dashboard Cite

show abstract

“…including an increase in repressive histone marks, a local change in nucleosome occupancy, or a general increase in histones' levels (Fiszbein et al, 2016;Gavin et al, 2017;Yoon et al, 2018). It was reported that the nuclei of ESCs macroscopically appear to contain less condensed chromatin, whereas well-defined foci of compact heterochromatin become evident in ESC-derived NPCs (Meshorer et al, 2006).…”

Section: Kinetic Coupling Is Enhanced In Neuronsmentioning

confidence: 99%

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes

et al. 2019

View full text Add to dashboard Cite

The rate of RNA polymerase II (RNAPII) elongation has an important role in the control of alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice. Focusing on neuronal differentiation as a model, we observed that slow elongation impairs development of the neural lineage from ESCs, which is accompanied by changes in AS and in gene expression along this pathway. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is greater in ESC‐differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development.

show abstract

“…17 . These epigenetic modifications are believed to be important to specify the lineage fidelity of different cell types during neurogenesis 15,[18][19][20][21] . For example, H3K27me3 is widely associated with important lineage genes and maintain them at a repressed but poised state in stem cells, as demonstrated by genome-wide mapping studies [22][23][24][25] .…”

mentioning

confidence: 99%

JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells

et al. 2020

View full text Add to dashboard Cite

Neurogenesis, a highly orchestrated process, entails the transition from a pluripotent to neural state and involves neural progenitor cells (NPCs) and neuronal/glial subtypes. However, the precise epigenetic mechanisms underlying fate decision remain poorly understood. Here, we delete KDM6s (JMJD3 and/or UTX), the H3K27me3 demethylases, in human embryonic stem cells (hESCs) and show that their deletion does not impede NPC generation from hESCs. However, KDM6-deficient NPCs exhibit poor proliferation and a failure to differentiate into neurons and glia. Mechanistically, both JMJD3 and UTX are found to be enriched in gene loci essential for neural development in hNPCs, and KDM6 impairment leads to H3K27me3 accumulation and blockade of DNA accessibility at these genes. Interestingly, forced expression of neuron-specific chromatin remodelling BAF (nBAF) rescues the neuron/glia defect in KDM6-deficient NPCs despite H3K27me3 accumulation. Our findings uncover the differential requirement of KDM6s in specifying NPCs and neurons/glia and highlight the contribution of individual epigenetic regulators in fate decisions in a human development model.

show abstract

Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence

Abstract: Yoon et al. review epigenetic and epitranscriptomic mechanisms that regulate the lineage specification of neural progenitor cells in the developing brain.

Cited by 74 publications

References 177 publications

Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes

JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells

Contact Info

Product

Resources

About