Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation

Lima, A. F.; May, G.; Colunga, J.; Pedreiro, S.; Paiva, A.; Ferreira, L.; Enver, T.; Iborra, F. J.; Pires Das Neves, R.

http://hdl.handle.net/10362/147022

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Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34 + umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.

Descrição

The authors would like to thank the financial support of FEDER through the program COMPETE POCI-01-0145-FEDER-007440 and by Portuguese funds through FCT (UID/NEU/04539/2013 and PTDC/SAU-ENB/113696/2009 to R.P.N.), FCT (SFRH/BD/51942/2012 to A.L.); Bloodwise and CRUK program grants to T.E. BFU2013-45918-R and BFU2016-79127-R to F.J.I.