TY  - JOUR
AU  - Ditzer, Nora
AU  - Senoglu, Ezgi
AU  - Kolodziejczyk, Annika
AU  - Schütze, Theresa M
AU  - Nikolaidi, Aikaterina
AU  - Küster, Karolin
AU  - Sameith, Katrin
AU  - Dietz, Sevina
AU  - Derihaci, Razvan P
AU  - Birdir, Cahit
AU  - Eugster, Anne
AU  - Karl, Mike O
AU  - Dahl, Andreas
AU  - Wimberger, Pauline
AU  - Baenke, Franziska
AU  - Peitzsch, Claudia
AU  - Albert, Mareike
TI  - Epigenome profiling identifies H3K27me3 regulation of extracellular matrix composition in human corticogenesis.
JO  - Neuron
VL  - nn
SN  - 0896-6273
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DKFZ-2025-01508
SP  - nn
PY  - 2025
N1  - epub
AB  - Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodeling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass-cytometry-based approach for the simultaneous single-cell analysis of more than 30 epigenetic marks. We identify Polycomb repressive complex 2 (PRC2)-mediated H3K27me3 as the modification with the strongest cell-type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation toward differentiation. Cell-type-specific profiling of H3K27me3 identified neuronal differentiation and extracellular matrix (ECM) genes in the human neocortex. PRC2 inhibition resulted in increased production of the ECM proteins Syndecan 1 and laminin alpha 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.
KW  - Polycomb repressive complex 2 (Other)
KW  - brain development (Other)
KW  - extracellular matrix (Other)
KW  - gene expression (Other)
KW  - histone methylation (Other)
KW  - human cortical organoid (Other)
KW  - human fetal cortex (Other)
KW  - neural stem cell (Other)
KW  - neurogenesis (Other)
KW  - single cell (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40701154
DO  - DOI:10.1016/j.neuron.2025.06.016
UR  - https://inrepo02.dkfz.de/record/303083
ER  -