RESUMEN
The majority of Musashi 1 (Msi1)positive cells derived from mouse embryonic stem cells (mESCs) are prone to differentiate into neural epitheliallike cells, and only a small proportion of Msi1positive cells differentiate into intestinal epitheliallike cells. Whether inhibiting the phosphatidylinositol 3kinase (PI3K) signaling of mESCs can promote the differentiation of Msi1positive cells into intestinal epitheliallike cells remains to be fully elucidated. In the present study, to inhibit PI3K signaling, mESCs were treated with LY294002. A pMsi1green fluorescence protein reporter plasmid was used to sort the Msi1positive cells from mESCs treated and untreated with LY294002 (5 µmol/l). The Msi1positive cells were hypodermically engrafted into the backs of nonobese diabetic/severe combined immunodeficient mice. The presence of neural and intestinal epitheliallike cells in the grafts was detected by reverse transcriptionquantitative polymerase chain reaction analysis and immunohistochemistry. Compared with the Msi1positive cells derived from mESCs without LY294002 treatment, Msi1positive cells derived from mESCs treated with LY294002 expressed higher levels of leucinerich repeatcontaining Gprotein coupled receptor, a marker of intestinal epithelial stem cells, and lower levels of Nestin, a marker of neural epithelial stem cells. The grafts from Msi1positive cells treated with LY294002 contained more intestinal epitheliallike tissues and fewer neural epitheliallike tissues, compared with those from untreated Msi1positive cells. LY294002 had the ability to promote the differentiation of mESCs into intestinal epitheliallike tissues. The Msi1positive cells selected from the cell population derived from mESCs treated with LY294002 exhibited more characteristics of intestinal epithelial stem cells than those from the untreated group.