Journal of Cancer Stem Cell Research
A population of very small embryonic-like stem cells (VSELs) in adult tissues, similar to embryonic stem cells (ESCs), is capable of differentiation in in vitro conditions and in vivo animal models into cells of all three germ lineages. The open chromatin structure of pluripotency genes and genomic imprinting related epigenetic mechanisms maintain their pluripotent and quiescent state, respectively. However, which transcription factors (TFs) are commonly expressed to maintain pluripotency in these SCs remains unknown. Here, by comparing the global transcriptome of VSELs with that of adult stem cells (SCs) [e.g., hematopoietic SC (HSCs)] or ESCs, we demonstrated that transcription factor CP2-like 1, a well-known naïve factor for ESCs, is highly expressed in murine VSELs. By analyzing a single-cell-level transcriptome database established from highly purified murine bone marrow (BM)-derived VSELs and HSCs as well as ESCs, we found that expression in a subset of TFs was shared by VSELs and ESCs. Among them, Tfcp2l1 was commonly expressed in murine VSELs and ESCs but not in HSCs and terminally differentiated BM mononuclear cells. During the differentiation of ESCs by forming an embryoid body or by treatment with retinoic acid, the expression of Tfcp2l1 decreased more rapidly than that of the typical pluripotency-associated TFs, including Oct4, Nanog, and Sox2. Ectopic expression of Tfcp2l1 in ESCs enforced expression of Oct4. Taken together, these results suggest that Tfcp2l1 functions as a common TF to regulate pluripotency in Oct4-expressing embryonic and adult pluripotent SCs and that dysregulation of Tfcp2l1 in adult SCs could initiate the transformation into cancer stem cells.