细胞生物学-自然2013-09-05 2:58 AM

Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT–MET mechanism for optimal reprogramming : Nature Cell Biology : Nature Publishing Group

Present practices for reprogramming somatic cells to induced pluripotent stem cells involve simultaneous introduction of reprogramming factors. Here we report that a sequential introduction protocol (Oct4–Klf4 first, then c-Myc and finally Sox2) outperforms the simultaneous one. Surprisingly, the sequential protocol activates an early epithelial-to-mesenchymal transition (EMT) as indicated by the upregulation of Slug and N-cadherin followed by a delayed mesenchymal-to-epithelial transition (MET). An early EMT induced by 1.5-day TGF-β treatment enhances reprogramming with the simultaneous protocol, whereas 12-day treatment blocks reprogramming. Consistent results were obtained when the TGF-β antagonist Repsox was applied in the sequential protocol. These results reveal a time-sensitive role of individual factors for optimal reprogramming and a sequential EMT–MET mechanism at the start of reprogramming. Our studies provide a rationale for further optimizing reprogramming, and introduce the concept of a sequential EMT–MET mechanism for cell fate decision that should be investigated further in other systems, both in vitro and in vivo.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

细胞生物学-自然

0 Following 0 Fans 0 Projects 20 Articles

SIMILAR ARTICLES

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated th

Read More

The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heav

Read More

The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is

Read More

Oligodendrocytes—the myelin-forming cells of the central nervous system—can be regenerated during adulthood. In adults, new oligodendrocytes originate

Read More

How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional anal

Read More

To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed

Read More

The lysosomal–autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the t

Read More

Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereb

Read More

Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in h

Read More

Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 (disc

Read More