Sox1 marks an activated neural stem/progenitor cell in the hippocampus

Abstract

SUMMARYThe dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born granular neurons, as well as a small number of mature hilar astrocytes. Furthermore, a subpopulation of Sox1-marked cells have long-term neurogenic potential, producing new neurons 3 months after inactivation of tetracycline transactivator. Remarkably, after 8 weeks of labeling and a 12-week chase, as much as 44% of all granular neurons in the dentate gyrus were derived from Sox1 lineagetraced adult neural stem/progenitor cells. The fraction of Sox1-positive cells within the radial astrocyte population decreases with age, correlating with a decrease in neurogenesis. However, expression profiling shows that these cells are transcriptionally stable throughout the lifespan of the mouse. These results demonstrate that Sox1 is expressed in an activated stem/progenitor population whose numbers decrease with age while maintaining a stable molecular program.

Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

“…Following this phase, differentiating iPSC cultures are characterized by the presence of cellular aggregates that include emerging neural rosettes. These cells express NSCs markers, NSCs markers, such as NESTIN, 17 SOX1, 21 and MUSASHI 22 (Fig. 2).…”

“…Change medium every other day. At day 5, replace NP selection medium with NP expansion medium and culture for 7 d After 3-5 d in NP expansion medium, 50-70% of colonies show the presence of cellular aggregates expressing NSCs markers NESTIN, 17 SOX1, 21 and MUSASHI 22 (Fig. 2).…”

Changes in hippocampal neurogenesis throughout early development

“…(O) The substantiating the crucial role of Sox2 in maintaining undifferentiated NPCs and hence neurogenesis in the adult hippocampus (Favaro et al, 2009;Ferri et al, 2004). Although Sox1 has also been documented in type-1 cells, its expression follows that of GFAP and Sox2 with a more restricted pattern, labeling only a subset of GFAPþ radial astrocytes and Sox2þ nonradial cells within the SGZ (Venere et al, 2012). Importantly, Sox1þ NPCs are responsible for producing most of the neuroblasts and, ultimately, adult-born new neurons.…”

“…We therefore explored age-related effects on the total size of earlier "progenitor" cells by quantifying changes in Sox1-expressing cell numbers within the hippocampal SGZ. Sox1 expression is critical in maintaining NPCs in a noncommitted state (Bylund et al, 2003), marking an activated population of early NPCs that gives rise to most, if not all, newborn granular neurons (Venere et al, 2012). Notably, as Sox1 directly activates Nestin-enhancer elements, Sox1 expression precedes the appearance of Nestin (Kan et al, 2004;Tanaka et al, 2004).…”

“…A new model reconciling both scenarios has been proposed with Sox1 playing, on initial expression, a role in maintaining division within the early progenitor cell pool but, on continued expression, leading to neuronal differentiation (Kan et al, 2007). Sox1-cells have recently been identified as a subset of early NPCs (also described as radial astrocytes and type-1 cells) activated to produce new astrocytes and neurons (Venere et al, 2012). Notably, Sox1 expression precedes the appearance of Nestin, in line with the essential role of SoxB1 proteins, i.e.…”