Abstract
In recent years, the need to derive sources of specialized cell types to be employed for cell replacement therapies and modeling studies has triggered a fast acceleration of novel cell reprogramming methods. In particular, in neuroscience, a number of protocols for the efficient differentiation of somatic or pluripotent stem cells have been established to obtain a renewable source of different neuronal cell types. Alternatively, several neuronal populations have been generated through direct reprogramming/transdifferentiation, which concerns the conversion of fully differentiated somatic cells into induced neurons. This is achieved through the forced expression of selected transcription factors (TFs) in the donor cell population. The reprogramming cocktail is chosen after an accurate screening process involving lists of TFs enriched into desired cell lineages. In some instances, this type of studies has revealed the crucial role of TFs whose function in the differentiation of a given specific cell type had been neglected or underestimated. Herein, we will speculate on how the in vitro studies have served to better understand physiological mechanisms of neuronal development in vivo.
Highlights
Over the years, crucial extrinsic and intrinsic mechanisms regulating the acquisition of cell fate during neural development have been elucidated
Weismann had suggested that genes whose function was no longer required might be lost or permanently inactivated in a specific cell type, seeding the concept that cell fate acquisition is an irreversible process being associated with loss of genetic material
Focusing our attention on the conditions where (i) ASCL1 or (ii) NEUROG2 were induced, we found that ASCL1 and NEUROG2 share a consistent number of direct targets (1863) maintaining many other exclusive (319+729 for ASCL1 and 811+5965 for NEUROG2) (Figure 1A)
Summary
Crucial extrinsic and intrinsic mechanisms regulating the acquisition of cell fate during neural development have been elucidated. To define a cell reprogramming gene cocktail, the TFs to be tested in the screening are chosen for their capability to impose that specific neuronal fate (master regulator genes) or among genes enriched in the target cell population, but not necessarily with their functions already addressed.
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