Intracellular signaling similarity reveals neural stem cell‐like properties of ependymal cells in the adult rat spinal cord

Abstract

Proliferation of ependymal cells of the adult spinal cord (SCEp cells) in the intact condition has been considered as a quite rare event. To visualize proliferating/proliferated SCEp cells, we used the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method to find that about two cells in the ependymal layer incorporated BrdU in a 10-μm-thick section. Because these two cells were not considered to undergo further proliferation, we analyzed the positioning and motility of two neighboring BrdU-incorporated proliferated cells and elucidated the tendency of the movement of SCEp cells to the outer side inside the ependymal layer. Even if it was rare, one of the proliferated cells in the ependymal layer differentiated into astrocytes. Gene introduction of Notch intracellular domain (NICD), a constitutively active form of Notch1, into SCEp cells demonstrated both increase in proliferation and induction of differentiation into astrocytes. Overexpression of Sox2 promoted proliferation in SCEp cells. The reaction of gene introduction of NICD and Sox2 indicates the similarity of intracellular signaling between SCEp cells and neural stem cells. Also, considering the fact that SCEp cells express these two factors in the intact condition, Notch and Sox2 are important for the cell fate control of SCEp cells in the intact condition.

RBP‐J deficiency promoted the proliferation and differentiation of CD133‐positive cells in both in vitro and in vivo studies

“…Shi et al (2012) and Kitada et al (2018) have demonstrated that the intracellular signals of ependymal cells are similar to those in the NSCs. Moreover, many signal transduction pathways are required for the neurogenesis of ependymal cells in adult mouse brain (Berg et al, 2011; Höglinger et al, 2004; Peng & Andersen, 2011; Shan et al, 2006; Zhao et al, 2003; Zhao & Janson, 2009).…”

“…Under physiological conditions, CD133‐expressing cells render quiescent NSC population in the ependymal layer of mammalian forebrain (Capela & Temple, 2002; Coskun et al, 2008; Doetsch et al, 1999; Spassky et al, 2005). In response to exposure to the vascular endothelial growth factor (VEGF) and bFGF, CD133‐positive cells are recruited, mitotically activated and then driven into the neurogenesis (Carlen et al, 2009; Kitada et al, 2018; Luo et al, 2015). Luo et al (2015) reported that the administration of VEGF was capable of activating CD133‐positive cells lining not only the LV but also the fourth ventricle, as well as eliciting their subsequent migration and differentiation.…”

“…Many studies have shown that CD133‐positive cells migrate away from the ependyma towards the dorsal part of the spinal cord following the neural injury, where they differentiate into the glial cells (Johansson et al, 1999; Kitada et al, 2018; Mothe & Tator, 2005). By constructing a recombinant plasmid prominin‐1‐mP2‐driven Cre, our studies revealed that the progeny of CD133‐positive cells gradually migrated toward the surrounding parenchyma from the 3 V‐ and Aq‐ependymal layer following an intranigral injection of 6‐OHDA (Xie et al, 2017).…”

RBP-J Deficiency Promoted The Proliferation and Differentiation of CD133-Positive Ependymal Cells In Vitro and In Vivo Studies

“…Some reports proposed that CD133-expressing ependymal cells in the SVZ and ependymal layer of mammalian forebrain rendered a quiescent NSC population under physiological conditions(Doetsch et al 1999;Capela and Temple 2002;Spassky et al 2005;Coskun et al 2008). In response to exposure to the vascular endothelial growth factor (VEGF) and bFGF, CD133-positive ependymal cells are recruited, mitotically activated and then driven into the neurogenesis(Carlen et al 2009;Luo et al 2015;Kitada et al 2018). Pfenninger et al (2011) reported that the administration of VEGF was capable of activating CD133positive ependymal cells lining not only the LV but also the fourth ventricle, as well as eliciting their subsequent migration and differentiation.…”

Wound repair, remodeling, and regeneration

“…provide an interesting topic: role of miRNA and immune cells in skin wound repair of mouse. As an article on “blastemal formation,” Kitada, Wakao, and Dezawa () have studied the proliferative potential of ependymal cells in rat spinal cord, which is a potential source to facilitate tissue repair after spinal cord injury in mammals. With articles on “recognition of positional information”, Hosoda et al.…”