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Journal Articles FEBS Letters Year : 2019

Stem cell reprogramming: blood, neurons, and beyond

Abstract

Reprogramming is the ability to change the fate of a cell to another one. A science(-fiction) technology that has long been unthinkable in the real world. Who would have ever bet that cell reprogramming could become a reality and rewrite some of the key rules of biology? During development, the fate of a cell and its differentiation program are dictated by a complex process involving specific transcription factors and epigenetic networks. This process appears to be ineluctable, since or even prior to its inception. However, in 1958, Sir John Gurdon demonstrated that reprogramming could be achieved by somatic cell nuclear transfer (SCNT). His pioneering experiments showed that nuclei from differentiated intestinal epithelial cells reacquired an embryonic state when transferred into enucleated frog eggs. The birth of normal tadpoles formally proved that the nucleus of differentiated cells contains all information needed to produce again all cell types in an organism. Almost 50 years later, Takahashi and Yamanaka demonstrated that the fate of a terminally differentiated cell is not ineluctable. In a groundbreaking study, they reprogrammed both murine and human fibroblasts to a stem cell fate by 'simply' introducing a few defined transcription factors (Oct4, Sox2, Klf4, c-Myc). Subcultivation of these reprogrammed fibroblasts led to the formation of induced pluripotent stem cells (iPSCs), which are morphologically and functionally almost identical to embryonic stem cells. In this way, it is possible to avoid embryo destruction and to reduce animal experimentation. Mature/specialized somatic cells can also be directly reprogrammed (or transdifferentiated) into other cell types with comparable levels of differentiation using lineage-specific transcription factors. This approach was introduced by Lassar in 1987 and, as it avoids the induction of pluripotency, is potentially safer than iPSC differentiation.

Dates and versions

hal-03977909 , version 1 (19-02-2023)

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Catherine Robin, Thierry Jaffredo, Holm Zaehres. Stem cell reprogramming: blood, neurons, and beyond. FEBS Letters, 2019, 593 (23), pp.3241 - 3243. ⟨10.1002/1873-3468.13660⟩. ⟨hal-03977909⟩
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