Novel alternative splicing variants of Klf4 display different capacities for self-renewal and pluripotency in mouse embryonic stem cells.

Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely while maintaining pluripotency. Krüppel-like factor (Klf) 4 is an important member of the Klf family that is known to play a key role in pluripotency and somatic cell reprogramming. However, the identification and functional comparison of Klf4 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we identified three novel alternative splicing variants of Klf4 in mESCs-mKlf4-108, mKlf4-375 and mKlf4-1482-that are distinct from the previously known mKlf4-1449. mKlf4-1449 and mKlf4-1482 may stimulate the growth of ESCs, while mKlf4-108 can only promote the growth of ESCs in LIFlow/serum conditions. In addition, both mKlf4-1449 and mKlf4-1482 can inhibit the differentiation of mESCs. However, the ability of mKlf4-1482 to promote self-renewal and inhibit differentiation is not as strong as that of mKlf4-1449. In contrast, both mKlf4-108 and mKlf4-375 may have the ability to induce endodermal differentiation. Taken together, we have identified for the first time the existence of alternative splicing variants of mKlf4 and have revealed their different roles, which provide new insights into the contribution of Klf4 to the self-renewal and pluripotency of mouse ESCs.