Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

Abstract

Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons and glial cells even at early passages, while early NSCs derived from clonal embryonic stem cells (ESCs)/ iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic NSCs and eliminated residual pluripotent cells that could form teratomas in vivo. We concluded that these directly induced NSCs were derived from partially reprogrammed cells, because dissociated ESCs/ iPSCs did not form neurospheres in this culture condition. These NSCs differentiated into both neurons and glial cells in vivo after being transplanted intracranially into mouse striatum. NSCs could also be directly induced from adult human fibroblasts. The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.

Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage

“…Thus, methods for reprogramming toward certain region-specific NPCs remain to be developed. Similar to previous studies (7,10,33), our iNPCs preferentially differentiated into astrocytes. Considering that BAM are neurogenic genes, preferential astrocytic differentiation is unexpected.…”

Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

“…However, in doing so, they largely lost the reprogramming efficacy, cell expandability/renewability (9,14), or the competence to generate myelin-forming cells in vitro or in vivo (11,(13)(14)(15)(21)(22)(23). It has been reported that reprogramming of fibroblasts to NPCs could be achieved using a single transcription factor, SOX2 (11).…”

Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Disease Modeling

“…To more rapidly induce NSCs from somatic cells, we generated NSCs from adult mouse fibroblasts that were partially reprogrammed by the introduction of the four Yamanaka factors (OSKM), which directs their differentiation into neural lineages 16) .…”