Different pluripotent states exist and have been established in vitro, including two‐cell‐like cells, expanded potential stem cells and extended pluripotent stem cells, naive embryonic stem cells, and primed epiblast stem cells. Compared with post implantation state, preimplantation state exhibits a more open chromatin structure, marked by DNA hypomethylation and enriched active histone modifications. This review summarizes recent contribution of single cell approaches, i.e., clonal fate mapping and single cell transcriptomics, to our understanding of NSCs heterogeneity as well as of their evolving spatial and temporal identities. Here, we illuminate a novel suppressor role of Tcf7l1 in regulating the self‐renewal of liver cancer stem cells by transcriptional inhibition of Nanog expression. Furthermore, we demonstrated for the first time that extrinsic factor IGF2 stimulation induces Tcf7l1 phosphorylation and protein degradation through MEK/ERK signal pathway, thus releasing the repression of Nanog expression and maintaining the self‐renewal of liver cancer stem cells. A model for the contribution of SET and MYND domain‐containing protein  to me endodermal lineage commitment of human embryonic stem cells is proposed. SET and MYND domain‐containing protein 2 activates the transcriptions of brachyury  mesodermal (EOMES ), mix paired‐like homeobox and goosefoot homeobox (GSC )