Figure 1.

Reprogramming is the process of switching a cell fate from a donor cell to a desired cell, needing orchestrated interactions between the intrinsic factors of endogenous genes and the extrinsic factors from culture microenvironment such as optimal cell plating density, glass coverslip, appropriate small molecules, and hypoxic conditions, e.g., 5% O₂. The donor cells are induced to cell cycle arrest at Gap 0 (G0) phase by transient serum starvation, and synchronized state to reenter cell cycle after re-feeding with serum. At Gap 1 (G1) phase, the donor cells are transduced with integrative or nonintegrative viral carriers, and returned to a transient Synthesis (S) phase. During S phase the exogenous transcription factors (TFs) from microarray data are transcribed and synthesized (black arrows), initiating endogenous pluripotency/multipotency gene expression (blue arrows). The integrative viral expression is within nucleus, and nonintegrative viral expression is in the cytoplasm. During Gap 2 (G2) phase, nucleosomes mature and histone biogenesis is repressed; the endogenous genes are further expressed to appropriate levels (blue arrows), simultaneously, the extrinsic viral TFs begin to be inhibited (red arrows). During Mitosis (M) phase, many TFs and chromatin binding proteins are ejected from the chromatin; the integrative viruses are gradually silenced, and the nonintegerative viral TFs are gradually removed from host cells (purple arrow). Finally, the desired cells such as induced pluripotent stem cells (iPSCs) and induced neural progenitor cells (iNPCs) are induced [13,26,33,40].