Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming

Area of Science:

• Stem cell biology
• Epigenetics
• Molecular biology

Background:

• Induced pluripotent stem cell (iPSC) generation using OCT4, SOX2, KLF4, and MYC (OSKM) is a revolutionary but inefficient and slow process.
• The underlying mechanisms of iPSC reprogramming potency remain largely unknown.
• Mesenchymal-to-epithelial transition (MET) is considered an early step in reprogramming.

Purpose of the Study:

• To investigate the role of ribosome biogenesis (RB) in the reprogramming process.
• To understand the timing and coordination of RB reprogramming relative to other pathways like MET.
• To correlate RB reprogramming dynamics with the efficiency and potency of iPSC generation.

Main Methods:

• Analysis of ribosome biogenesis (RB) global enrichment in human embryonic stem cells versus fibroblasts.
• Assessment of RB network reprogramming dynamics during OSKM-induced pluripotency.
• Comparison of RB reprogramming kinetics with the initiation of mesenchymal-to-epithelial transition (MET).

Main Results:

• Ribosome biogenesis (RB) is globally enriched in human embryonic stem cells compared to fibroblasts.
• The RB network is reprogrammed rapidly and in a coordinated manner during OSKM-induced pluripotency.
• Robust RB reprogramming occurs independently of substantial MET initiation.
• This rapid RB reprogramming was consistent across different fibroblast lines.

Conclusions:

• Rapid and coordinated ribosome biogenesis (RB) reprogramming is a key feature of efficient iPSC generation.
• The observed RB reprogramming dynamics align with the potency aspect of OSKM-mediated reprogramming.
• RB reprogramming is a crucial, early, and coordinated event that contrasts with the overall inefficiency of iPSC generation.