RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1+ Roof-Plate-Derived Cells

Abstract

Summary Anamniotes, rodents, and young humans maintain neural stem cells in the ependymal zone (EZ) around the central canal of the spinal cord, representing a possible endogenous source for repair in mammalian lesions. Cell diversity and genes specific for this region are ill defined. A cellular and molecular resource is provided here for the mouse and human EZ based on RNA profiling, immunostaining, and fluorescent transgenic mice. This uncovered the conserved expression of 1,200 genes including 120 transcription factors. Unexpectedly the EZ maintains an embryonic-like dorsal-ventral pattern of expression of spinal cord developmental transcription factors (ARX, FOXA2, MSX1, and PAX6). In mice, dorsal and ventral EZ cells express Vegfr3 and are derived from the embryonic roof and floor plates. The dorsal EZ expresses a high level of Bmp6 and Gdf10 genes and harbors a subpopulation of radial quiescent cells expressing MSX1 and ID4 transcription factors.

Dynamic cell interactions allow spinal cord regeneration in zebrafish

“…ERGs also generate new neurons in the injured spinal cord. Similar ventricular stem cells exist in mammals [17,18], but they only contribute cells to the glial scar [19]. The new neurons in adult zebrafish are derived from different ventricular domains of ERGs that are reminiscent of progenitor domains in the developing neural tube and new neurons are integrated into the spinal network [20].…”

Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells

“…Laser microdissection of the ependymal region in sham and injured spinal cord (72h post injury, 6 animals each condition) were performed exactly as described in details in (Ghazale et al 2019) . After dissection, part of the thoracic spinal cord containing the needle insertion sites was selected and flashed frozen in N2 without chemical fixation.…”

Unlocking the paradoxical endogenous stem cell response after spinal cord injury

“…25 Recently, RNA profiling has further revealed an embryonic-like dorsal to ventral pattern of gene expression of key regulatory transcription factors within the ependymal zone. 21 27 Moreover, adult ependymal cells appear to maintain Wnt/beta-catenin signaling activity which may be necessary for proliferation and stem cell maintenance. 28 Elucidating the influence of injury-induced environmental cues on gene expression is an important step in harnessing the regenerative potential of endogenous NSPCs.…”