Abstract
Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.
Highlights
They are broadly classified into two main groups: embryonic stem (ES) cells, which are derived from the inner cell masses (ICMs) of mammalian blastocysts, and induced pluripotent stem cells, which can be generated from somatic cells by introducing defined transcription factors, such as Oct[4], Sox[2], Klf[4] and cMyc.[3] iPS cells are molecularly and functionally similar to ES cells.[4,5]
Trib[2] regulates the efficiency of somatic cell reprogramming into iPS cells To investigate whether Trib[2] contributes to the reprogramming process in the generation of iPS cells from somatic cells, we examined the effect of Trib[2] knockdown during the generation of iPS cells from mouse mouse embryonic fibroblasts (MEFs)
The expression levels of Trib[2] in mouse ES (mES) cells and differentiated embryoid bodies (EBs) resemble those of Oct[4], an important regulator of pluripotency in undifferentiated ES cells
Summary
Pluripotent cells have drawn major attention due to their nearly unlimited self-renewal potential and their ability to differentiate into all types of cells in the body.[1,2] They are broadly classified into two main groups: embryonic stem (ES) cells, which are derived from the inner cell masses (ICMs) of mammalian blastocysts, and induced pluripotent stem (iPS) cells, which can be generated from somatic cells by introducing defined transcription factors, such as Oct[4], Sox[2], Klf[4] and cMyc.[3] iPS cells are molecularly and functionally similar to ES cells.[4,5] ES cells and iPS cells are attractive for therapeutic applications due to their unlimited potential to self-renew and differentiate.[6,7,8] an understanding of the molecular mechanism underlying pluripotency induction and maintenance has a significant impact on basic biology and on clinical applications for treating various diseases using regenerative medicine.Tribbles homolog 2 (Trib2) is a member of the Tribbles family, and members of this family act as adaptors or scaffolds in signaling pathways.[9]. Pluripotent cells have drawn major attention due to their nearly unlimited self-renewal potential and their ability to differentiate into all types of cells in the body.[1,2] They are broadly classified into two main groups: embryonic stem (ES) cells, which are derived from the inner cell masses (ICMs) of mammalian blastocysts, and induced pluripotent stem (iPS) cells, which can be generated from somatic cells by introducing defined transcription factors, such as Oct[4], Sox[2], Klf[4] and cMyc.[3] iPS cells are molecularly and functionally similar to ES cells.[4,5] ES cells and iPS cells are attractive for therapeutic applications due to their unlimited potential to self-renew and differentiate.[6,7,8] an understanding of the molecular mechanism underlying pluripotency induction and maintenance has a significant impact on basic biology and on clinical applications for treating various diseases using regenerative medicine. Trib[2] is implicated in multiple important cellular processes, its relevance in pluripotency regulation has not been reported
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
