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

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

doi:10.1038/s41598-018-25517-2

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

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

Faculdade de Ciências e Tecnologia (FCT)

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Abstract

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.

Original language	English
Article number	25517
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-25517-2
Publication status	Published - 1 Dec 2018

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Osmotic modulation of chromatinFinal published version, 2.46 MBLicence: CC BY

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title = "Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation",

abstract = " 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. ",

author = "Lima, {A. F.} and G. May and J. Colunga and S. Pedreiro and A. Paiva and L. Ferreira and T. Enver and Iborra, {F. J.} and {Pires Das Neves}, R.",

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AU - May, G.

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AU - Paiva, A.

AU - Ferreira, L.

AU - Enver, T.

AU - Iborra, F. J.

AU - Pires Das Neves, R.

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AB - 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.

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

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