Identification of a discrete subpopulation of spinal cord ependymal cells with neural stem cell properties

Ependymal cell maturation is heterogeneous and ongoing in the mouse spinal cord and dynamically regulated in response to injury

“…This study focused on Tnfrsf19 (Troy)-expressing ependymal cells, some of which displayed extraordinary neural stem cell capabilities in vitro . However, consistent with RNAscope data in Stenudd et al, 2022, we found that cells of every ependymal subtype and state identified in our comprehensive scRNA-seq dataset express Tnfrsf19 (Figure S6). This indicates that Troy-CreER recombined cells include ependymal cells with distinct identities, and so it remains unclear which of these possess neural stem cell properties.…”

“…While some ependymal cells in the spinal cord proliferate slowly or rarely postnatally and retain the ability to self-renew and give rise to specialised cell types in response to injury, brain ependymal cells are postmitotic and lack neural stem cell potential (Alfaro-Cervello et al, 2012; Carlén et al, 2009; Li et al, 2018; Meletis et al, 2008; Shah et al, 2018; Spassky et al, 2005; Stenudd et al, 2022). To uncover transcriptomic differences that may map to these important differences between spinal cord and brain ependymal cells, we integrated our 10x ependymal cell dataset from young mice with data from Zeisel and colleagues (Zeisel et al, 2018), which includes ependymal cell transcriptomes from across the CNS (Figure S5A and B) (Methods).…”

“…As we were preparing this paper for publication further scRNA-seq evidence for ependymal cell downregulation of cilia-related genes after injury was reported (Stenudd et al, 2022). This study focused on Tnfrsf19 (Troy)-expressing ependymal cells, some of which displayed extraordinary neural stem cell capabilities in vitro .…”

“…This contrasts with the more rapid maturation of brain ependymal cells, which in the mouse is complete two weeks after birth (Spassky et al, 2005). Importantly, while mature spinal cord cells and brain ependymal cells share defining molecular features (Figure 5), it is clear that some spinal cord ependymal cells uniquely behave as neural stem cells (Barnabé-Heider et al, 2010; Meletis et al, 2008; Shah et al, 2018; Stenudd et al, 2022). Our findings therefore raised the possibility that this elusive neural stem potential resides within the immature lateral cell fraction and is lost as cells fully mature.…”

“…While it is well-established that in the mouse brain ependymal cells are postmitotic and the neural stem cell potential resides in subependymal type B1 cells (Capela and Temple, 2002; Chiasson et al, 1999; Doetsch et al, 1997, 1999; Shah et al, 2018; Spassky et al, 2005), ependymal cells in the adult spinal cord can be found proliferating occasionally and at least some retain neural stem cell potential. From axolotls and zebrafish to mice, spinal cord ependymal cells can re-enter the cell cycle to self-renew and give rise to specialised cell types in response to injury and in culture (Barnabé-Heider et al, 2010; Bauchet et al, 2013; Dromard et al, 2008; Johansson et al, 1999; Lacroix et al, 2014; Li et al, 2018; Llorens-Bobadilla et al, 2020; Meletis et al, 2008; Mothe et al, 2011; Pfenninger et al, 2010; Stenudd et al, 2022). Ependymal cells in the human spinal cord have not been observed proliferating (Alfaro-Cervello et al, 2014; Dromard et al, 2008; Paniagua-Torija et al, 2018), but also display neural stem cell features when cultured in vitro (Dromard et al, 2008; Hugnot, 2013; Mothe et al, 2011).…”