Imprinted Genes That Regulate Early Mammalian Growth Are Coexpressed in Somatic Stem Cells

Abstract

Lifelong, many somatic tissues are replenished by specialized adult stem cells. These stem cells are generally rare, infrequently dividing, occupy a unique niche, and can rapidly respond to injury to maintain a steady tissue size. Despite these commonalities, few shared regulatory mechanisms have been identified. Here, we scrutinized data comparing genes expressed in murine long-term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes. Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations. These imprinted genes were also predominantly expressed in stem/progenitor cells of the adult epidermis and skeletal muscle in mice, relative to their differentiated counterparts. The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis.

A systems-level approach to parental genomic imprinting: the imprinted gene network includes extracellular matrix genes and regulates cell cycle exit and differentiation

“…Following early observations suggesting coregulation of a small number of IGs (Hayashida et al 1997;Yan et al 2003), we showed that a subset of 15 IGs is frequently coexpressed (Varrault et al 2006), which was confirmed by other groups (Lui et al 2008;Berg et al 2011;Zacharek et al 2011). The present study identified significantly more coexpression among IGs by using broader and more varied data sets; e.g., the Gemma and COXPRESdb databases comprise data sets from the nervous system, which was underrepresented in the TMM database originally explored.…”

H19 controls reactivation of the imprinted gene network during muscle regeneration

“…These genes belong to an imprinted gene network described by several authors (Varrault et al, 2006;Lui et al, 2008;Berg et al, 2011;Al Adhami et al, 2015). Our results suggest that H19 controls growth of the embryo through a balanced expression of imprinted genes.…”

“…This is accompanied by an important self-renewal step to help maintain this stem cell population (Sambasivan and Tajbakhsh, 2007;White et al, 2010). Interestingly, the IGN appears to play a role in the satellite cells as shown by the expression of many imprinted genes in these cells (Yan et al, 2003;Berg et al, 2011;Al Adhami et al, 2015).…”

Defining skeletal muscle resident progenitors and their cell fate potentials

“…The observation that all these progenitors express PW1 suggests a common regulatory program. A recent report has shown that PW1 is one member of a group of ten parentally imprinted genes that are expressed in several somatic stem cell lineages in both mice and humans (Berg et al, 2011;Pannérec et al, 2012). We note that PW1 participates in both intrinsic (p53) and extrinsic (inflammatory cytokine signaling) cell stress responses (Relaix et al, 2000;Relaix et al, 1998;Schwarzkopf et al, 2006), which might reflect a shared response mechanism to cell stress in stem cells.…”