Engineering more efficient ways to create iPSCs by dissecting the OCT4 transcription factor

Researchers identified regions of the OCT4 transcription factor which, when engineered can create new reprogramming factors that are more efficient and specific for iPSC generation.

three molecular diagrams of reprogramming factors which look like curly squiggles with sections of tinner yellow and thicker blue
Cartoon 3D representation of OCT4 showing how engineered reprogramming factors were established.

A key challenge in regenerative medicine is obtaining medically relevant cell types to repair damaged organs and tissues such as the heart, eyes, spine, and brain. 

A promising solution is reprogramming a patient’s own cells into induced pluripotent stem cells (iPSCs) using four transcription factors: OCT4, SOX2, KLF4, and cMYC. These iPSCs can differentiate into any cell type in the body. However, this process is inefficient and often produces partially reprogrammed cells with compromised functions. Research at the IRR aims to engineer reprogramming factors that are more efficient and specific for iPSCs. 

In this study, researchers systematically dissected the transcription factor OCT4 and identified small areas within its disordered regions that serve specific reprogramming functions. They termed these short linear peptides essential for reprogramming as SLiPERs. They utilised these SLiPERs to engineer novel reprogramming factors that are more efficient and specific for iPSC generation. 

 

This is exciting because similar experiments with SOX2, KLF4, and cMYC could uncover other reprogramming-specific modules, ultimately helping to engineer optimal reprogramming factors, potentially leading to better cell therapies or better models of disease

Tags

CRM