Affiliation:
1. Epigenetics, Babraham Institute, Cambridge CB22 3AT, UK
2. Bioinformatics Facility, Babraham Institute, Cambridge CB22 3AT, UK
Abstract
During mammalian embryo development, pluripotent epiblast cells diversify into the three primary germ layers, which will later give rise to all fetal and adult tissues. These processes involve profound transcriptional and epigenetic changes that require precise coordination. Peptidylarginine deiminase IV (PADI4) is a transcriptional regulator that is strongly associated with inflammation and carcinogenesis but whose physiological roles are less well understood. We previously found that
Padi4
expression is associated with pluripotency. Here, we examined the role of PADI4 in maintaining the multi-lineage differentiation potential of mouse embryonic stem (ES) cells. Using bulk and single-cell transcriptomic analyses of embryoid bodies (EBs) derived from
Padi4
knock-out (
Padi4-KO
) mouse ES cells, we find that PADI4 loss impairs mesoderm diversification and differentiation of cardimyocytes and endothelial cells. Additionally,
Padi4
deletion leads to concerted downregulation of genes associated with polarized growth, sterol metabolism and the extracellular matrix (ECM). This study indicates a requirement for
Padi4
in the specification of the mesodermal lineage and reports the
Padi4
associated transcriptome, providing a platform for understanding the physiological functions of
Padi4
in development and homeostasis.
This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Funder
Royal Society
Wellcome
Biotechnology and Biological Sciences Research Council
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology
Cited by
2 articles.
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1. Transcriptomic analysis of PADI4 target genes during multi-lineage differentiation of embryonic stem cells;Philosophical Transactions of the Royal Society B: Biological Sciences;2023-10-02
2. Citrullination: new tricks for an old mod;Philosophical Transactions of the Royal Society B: Biological Sciences;2023-10-02