TY - JOUR
T1 - Variable allelic expression of imprinted genes at the
AU - Claxton, Michael
AU - Pulix, Michela
AU - Seah, Michelle K Y
AU - Bernardo, Ralph
AU - Zhou, Peng
AU - Aljuraysi, Sultan
AU - Liloglou, Triantafillos
AU - Arnaud, Philippe
AU - Kelsey, Gavin
AU - Messerschmidt, Daniel M
AU - Plagge, Antonius
PY - 2022/10/12
Y1 - 2022/10/12
N2 - Genomic imprinting is an epigenetic process through which genes are expressed in a parent-of-origin specific manner resulting in mono-allelic or strongly biased expression of one allele. For some genes, imprinted expression may be tissue-specific and reliant on CTCF-influenced enhancer-promoter interactions. The imprinting cluster is associated with neurodevelopmental disorders and comprises canonical imprinted genes, which are conserved between mouse and human, as well as brain-specific imprinted genes in mouse. The latter consist of , and , which have a maternal allelic expression bias of ∼75% in brain. Findings of such allelic expression biases on the tissue level raise the question of how they are reflected in individual cells and whether there is variability and mosaicism in allelic expression between individual cells of the tissue. Here we show that and are not imprinted in hippocampus-derived neural stem cells (neurospheres), while retains its strong bias of paternal allele expression. Upon analysis of single neural stem cells and differentiated neurons, we find not uniform, but variable states of allelic expression, especially for and . These ranged from mono-allelic paternal to equal bi-allelic to mono-allelic maternal, including biased bi-allelic transcriptional states. Even expression deviated from its expected paternal allele bias in a small number of cells. Although the cell populations consisted of a mosaic of cells with different allelic expression states, as a whole they reflected bulk tissue data. Furthermore, in an attempt to identify potential brain-specific regulatory elements across the locus, we demonstrate tissue-specific and general silencer activities, which might contribute to the regulation of its imprinted expression bias. [Abstract copyright: Copyright © 2022 Claxton, Pulix, Seah, Bernardo, Zhou, Aljuraysi, Liloglou, Arnaud, Kelsey, Messerschmidt and Plagge.]
AB - Genomic imprinting is an epigenetic process through which genes are expressed in a parent-of-origin specific manner resulting in mono-allelic or strongly biased expression of one allele. For some genes, imprinted expression may be tissue-specific and reliant on CTCF-influenced enhancer-promoter interactions. The imprinting cluster is associated with neurodevelopmental disorders and comprises canonical imprinted genes, which are conserved between mouse and human, as well as brain-specific imprinted genes in mouse. The latter consist of , and , which have a maternal allelic expression bias of ∼75% in brain. Findings of such allelic expression biases on the tissue level raise the question of how they are reflected in individual cells and whether there is variability and mosaicism in allelic expression between individual cells of the tissue. Here we show that and are not imprinted in hippocampus-derived neural stem cells (neurospheres), while retains its strong bias of paternal allele expression. Upon analysis of single neural stem cells and differentiated neurons, we find not uniform, but variable states of allelic expression, especially for and . These ranged from mono-allelic paternal to equal bi-allelic to mono-allelic maternal, including biased bi-allelic transcriptional states. Even expression deviated from its expected paternal allele bias in a small number of cells. Although the cell populations consisted of a mosaic of cells with different allelic expression states, as a whole they reflected bulk tissue data. Furthermore, in an attempt to identify potential brain-specific regulatory elements across the locus, we demonstrate tissue-specific and general silencer activities, which might contribute to the regulation of its imprinted expression bias. [Abstract copyright: Copyright © 2022 Claxton, Pulix, Seah, Bernardo, Zhou, Aljuraysi, Liloglou, Arnaud, Kelsey, Messerschmidt and Plagge.]
KW - neurosphere
KW - Peg13
KW - Ago2
KW - neural stem cell
KW - Trappc9
KW - single-cell analysis
KW - genomic imprinting
KW - allelic expression
U2 - 10.3389/fcell.2022.1022422
DO - 10.3389/fcell.2022.1022422
M3 - Article (journal)
C2 - 36313557
SN - 2296-634X
VL - 10
SP - 1022422
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
ER -