Oct4-Sox2-Nanog transcriptional networks are critical for the maintenance of embryonic stem (ES) cell self-renewal and induction of pluripotency. However, in transcription factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), Nanog is initially dispensable and Oct4 remains the sole factor that could not be substituted/omitted. Here, we show that mouse fibroblasts could be reprogrammed into iPSCs by Nanog and Bmi1, which replaces Sox2, Klf4, and c-Myc, in the absence of Oct4. Furthermore, we show that in the presence of shh agonists (oxysterol and purmophamine), which replaces the function of Bmi1, a single transcription factor, Nanog is sufficient to reprogram mouse fibroblasts into iPSCs. Nanog-induced iPSCs resemble mESCs in terms of morphology, global gene expression profiles, epigenetic status and pluripotency both in vitro and in vivo. These findings support that Nanog can replace the Oct4 for the somatic cell reprogramming and underlie the mechanisms of Nanog in reprogramming process.
|Number of pages
|Biochemical and biophysical research communications
|Published - 2013 Feb 15
Bibliographical noteFunding Information:
This research was supported by a Grant from the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government (Ministry of Education, Science and Technology) (No. 2012-0006451 ), and by a Grant from the Korean Health Technology R&D Project, funded by the Ministry of Health and Welfare (No. A120392 ).
- Sonic hedgehog
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology