Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells

Figure 5

Model of in vitro neural differentiation in ESCs in presence and absence of Rybp. (a) Differentiation of wild type ESCs towards matured cell types of the CNS in the presence of Rybp. Pluripotent ESCs express key pluripotency markers (e.g., Oct4, Nanog) in undifferentiated state, which are gradually decreasing through in vitro neural differentiation. Parallel with this, early neural markers (Pax6, Nestin) are upregulated in NSCs, which will confer reduced proliferative and high differentiation capacity to the cells. On the other hand, in the presence of Rybp, upregulation of Plagl1 helps to facilitate late neural differentiation and inhibits cell proliferation, which will facilitate the generation of terminally differentiated neural cell types (N, OC, and AC). By the progression of neural differentiation, NPCs will differentiate further and start to express markers of specialized neural cell types (Tuj1, NeuN, Olig2, and Gfap). (b) Differentiation of pluripotent ESCs towards matured cell types of the CNS is impaired in the absence of Rybp. During neural differentiation early neural markers (Pax6, Nestin) exhibit elevated expression level in the rybp null mutants. These will facilitate the generation of a bigger pool of NPCs with higher proliferative capacity. On the other hand, in the absence of Rybp, Plagl1 expression is defective, which also contributes to increased proliferative and decreased differentiation capacity of the NPCs. As a result, the formation of terminally differentiated neural cell types (N, OC, and AC) will be impaired in the lack of functional Rybp. ESC: embryonic stem cell; NSC: neural stem cell; NPC: neural progenitor cell; N: neuron; OC: oligodendrocyte; AC: astrocyte; RA: retinoic acid; CNS: central nervous system.

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