Spinal cord regeneration — the origins of progenitor cells for functional rebuilding

Radial glia and radial glia-like cells: Their role in neurogenesis and regeneration

“…In addition to the neurogenic regenerative potentials of RGLCs, there are also parallels in the processes by which RGLCs in different species or different regions of the CNS respond to injury. Specifically, changes observed in their radial morphology and, at the molecular level, in their gene expression profile point out toward a degree of dedifferentiation, where a mature cell reverts into a progenitor/stem cell phenotype as described by Walker and Echeverri (2022) . Dedifferentiation allows cells to enter the cell cycle and give rise to new tissue cells.…”

“…The nomenclature used to name these cells mostly depends on the species or on the anatomical region where they are found. For example, radial ependymoglial cells, Bergmann radial glia, and Müller glial cells are terms used to describe them in the spinal cord, cerebellum, and retina, respectively ( Goldman, 2014 ; Gao et al, 2021 ; Walker and Echeverri, 2022 ). Similarly, cells that share these characteristics in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammals have been interchangeably addressed in the literature as neural stem cells (NSC), RGLC, and radial astrocyte (RA) ( Gebara et al, 2016 ; Berg et al, 2018 ; Joven and Simon, 2018 ; Lust and Tanaka, 2019 ; Obernier and Alvarez-Buylla, 2019 ; Urbán et al, 2019 ; Zambusi and Ninkovic, 2020 ).…”

“…Our focus is mainly on injury-induced neurogenesis and the mechanisms by which adult organisms activate neurogenesis in response to injury. Similar to the processes of cellular homeostasis or regeneration in other organs or tissues, new nerve cells originate from: (1) a reservoir of stem cells that can proliferate and differentiate to maintain tissue physiology or restore and repair an injury site or (2) by dedifferentiation, where a cell population reverts to a less-differentiated state by losing some of their differentiated properties ( Tanaka, 2016 ; Yao and Wang, 2020 ; Walker and Echeverri, 2022 ). These cells can eventually divide and produce replacement cells for the organ or tissue in question.…”

“…(3) A third mechanism has been proposed where tissues can generate new cells via trans-differentiation. In this case, similar to dedifferentiation, the cells lose their specific phenotypic characteristics and then acquire the phenotype of a different cell type without transiting through a “less differentiated stage” ( Walker and Echeverri, 2022 ).…”

“…In addition, several markers associated with RGCs are expressed by the proliferating cells following spinal cord injury ( Hui et al, 2015a ). After injury, these cells have been shown to retract their radial processes, proliferate and differentiate to form new spinal cord neurons ( Reimer et al, 2008 ; Ribeiro et al, 2017 ; Cura Costa et al, 2021 ; Klatt Shaw et al, 2021 ; Walker and Echeverri, 2022 ). In fact, some researchers have suggested that these RGLCs undergo dedifferentiation during regeneration, as can be determined by the changes in cell morphology, the loss of the radial extensions, and the differential expression of genes associated with neural stem cell properties ( Walder et al, 2003 ; Ribeiro et al, 2017 ; Walker and Echeverri, 2022 ).…”