Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds

Abstract

Recently, we reported a chemical approach to generate pluripotent stem cells from mouse fibroblasts. However, whether chemically induced pluripotent stem cells (CiPSCs) can be derived from other cell types remains to be demonstrated. Here, using lineage tracing, we first verify the generation of CiPSCs from fibroblasts. Next, we demonstrate that neural stem cells (NSCs) from the ectoderm and small intestinal epithelial cells (IECs) from the endoderm can be chemically reprogrammed into pluripotent stem cells. CiPSCs derived from NSCs and IECs resemble mouse embryonic stem cells in proliferation rate, global gene expression profile, epigenetic status, self-renewal and differentiation capacity, and germline transmission competency. Interestingly, the pluripotency gene Sall4 is expressed at the initial stage in the chemical reprogramming process from different cell types, and the same core small molecules are required for the reprogramming, suggesting conservation in the molecular mechanism underlying chemical reprogramming from these diverse cell types. Our analysis also shows that the use of these small molecules should be fine-tuned to meet the requirement of reprogramming from different cell types. Together, these findings demonstrate that full chemical reprogramming approach can be applied in cells of different tissue origins and suggest that chemical reprogramming is a promising strategy with the potential to be extended to more initial types.

Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming

“…We previously demonstrated that, in contrast to OSKMinduced reprogramming, the first cornerstone of chemical reprogramming is the formation of plastic XEN-like cells marked by Gata4, Gata6, and Sox17, which resemble the extraembryonic endoderm (XEN) cells of the blastocyst at the preimplantation stage in terms of transcriptome, developmental ability, and reprogramming potential Ye et al, 2016;Zhao et al, 2015Zhao et al, , 2016. Recently, our findings were also confirmed by other groups (Cao et al, 2018;Ping et al, 2018) using a similar small molecule cocktail that targets the same pathways identified by our group.…”

Cell fate conversion—from the viewpoint of small molecules and lineage specifiers

“…In addition to mesoderm‐origin fibroblasts, neural stem cells originating from the ectoderm and intestinal epithelial cells originating from the endoderm can also be reprogrammed to pluripotency by the fine‐tuning of the small‐molecule cocktail . Notably, through similar gene expression analysis, genetic approaches and fluorescence‐activated cell sorting (FACS) experiments carried out in fibroblasts, we found that, although chemical reprogramming processes were initiated from cells of different germ layers, they underwent the same XEN‐like intermediate state during the induction of CiPSCs, implying the generality of the XEN‐like state during chemical reprogramming towards pluripotency …”

The modification of mitochondrial energy metabolism and histone of goat somatic cells under small molecules compounds induction

“…Although the use of direct protein mediated method could completely avoid this problem, the reprogramming efficiency was very low (Kim et al, ), so there was not much practical value. Currently, induced pluripotent stem cells (CiPSC) could be successfully reprogrammed by small‐molecule compounds from mouse somatic cells which had higher reprogramming efficiency and no exogenous genes integration (Hou et al, ; Kang et al, ; Yang et al, ; Ye et al, ). It could be the most ideal method for iPSCs generation.…”