Journal
SCIENCE
Volume 364, Issue 6440, Pages 547-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aav2522
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Funding
- Swiss National Science Foundation
- Carigest Foundation
- FRS-FNRS [EOS O019118F-RG36, CDR J.0028.18, PDR T.0073.15]
- Fonds Leon Fredericq
- Fondation Medicale Reine Elisabeth
- Fondation Simone et Pierre Clerdent
- IST Austria institutional funds
- European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Program [725780 LinPro]
- Fondation privee des HUG
- National Center of Competence in Research (NCCR) Synapsy
- FWF Hertha Firnberg Program grant [T 1031-BBL]
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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.
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