Question

How does epigenetic play a role in reprogramming reprogramming of somatic cells into iPS cells? Does retroviral vectors impact the role?

Why is there a concern about the differentiation potential of iPS cells if they have the same RNA profile as embryonic stem cells? Do epigenetics play a role in this?

Answer 1

-->

- Reprogramming of somatic cells to induced pluripotency using defined transcription factors is predominantly an epigenetic phenomenon. Epigenetic as well as (single-cell) transcriptomic analyses on isolated reprogramming intermediates en route to induced pluripotency have generated invaluable mechanistic insights into the process of cell fate specification and transition.

Reprogramming requires global remodeling of somatic cell chromatin from a highly condensed state (heterochromatin) to a more dispersed conformation (euchromatin). Whereas heterochromatin reorganization occurs early in reprogramming, the establishment of euchromatin features constitutes a relatively late event. Heterochromatin-associated H3K9 methylation constitutes an important epigenetic barrier to cellular reprogramming.Trithorax and Polycomb group proteins play an indispensable role in specifying and maintaining pluripotent cell identity.

- YES, retroviral impact the role,they are transcriptionally silent in pluripotent stem cells. This feature has been potently applied in studies that reprogramsomatic cells into induced pluripotent stem (iPS) cells. By delivering the four Yamanaka factors in retroviral vectors, high expression isobtained in fibroblasts to induce the pluripotent state. Partial reprogramming generates Class I iPS cells that express the viral transgenes andendogenous pluripotency genes. Full-reprogramming in Class II iPS cells silences the vectors as the endogenous genes maintain thepluripotent state.

-->

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are pluripotent stem cells (PSCs) that have two distinct features: the ability to proliferate in the undifferentiated state (self-renewal) and the potential to differentiate in response to differentiation stimuli. However, the potential to differentiate can only be verified by exposing PSCs to external differentiation signals. Prediction of the differentiation potential while maintaining PSCs in the undifferentiated state is particularly important for clinical applications of PSC-derived cell products because inclusion of undifferentiated cells or differentiation-resistant cells in the final PSC-derived cell product may lead to the development of tumors after transplantation .