[en] In vitro corticogenesis from embryonic stem cells (ESCs) is an attractive model of cortical development and a promising tool for cortical therapy. It is unknown to which extent epigenetic mechanisms crucial for cortex development and function, such as parental genomic imprinting, are recapitulated by in vitro corticogenesis. Here, using genome-wide transcriptomic and methylation analyses on hybrid mouse tissues and cells, we find a high concordance of imprinting status between in vivo and ESC-derived cortices. Notably, in vitro corticogenesis strictly reproduced the in vivo parent-of-origin-dependent expression of 41 imprinted genes (IGs), including Mest and Cdkn1c known to control corticogenesis. Parent-of-origin-dependent DNA methylation was also conserved at 14 of 18 imprinted differentially methylated regions. The least concordant imprinted locus was Gpr1-Zdbf2, where the aberrant bi-allelic expression of Zdbf2 and Adam23 was concomitant with a gain of methylation on the maternal allele in vitro. Combined, our data argue for a broad conservation of the epigenetic mechanisms at imprinted loci in cortical cells derived from ESCs. We propose that in vitro corticogenesis helps to define the still poorly understood mechanisms that regulate imprinting in the brain and the roles of IGs in cortical development.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bouschet, Tristan
Dubois, Emeric
Reynès, Christelle
Kota, Satya K.
Rialle, Stéphanie
Maupetit-Méhouas, Stéphanie
Pezet, Mikael
Le Digarcher, Anne
Nidelet, Sabine
Demolombe, Vincent
Cavelier, Patricia
Meusnier, Céline
Maurizy, Chloé ; Université de Liège - ULiège > GIGA Stem Cells - Medical Chemistry
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