DNA hypermethylation in somatic cells correlates with higher reprogramming efficiency

María J. Barrero; María Berdasco; Ida Paramonov; Josipa Bilic; Marianna Vitaloni; Manel Esteller; Juan Carlos Izpisua Belmonte

doi:10.1002/stem.1138

DNA hypermethylation in somatic cells correlates with higher reprogramming efficiency

María J. Barrero, María Berdasco, Ida Paramonov, Josipa Bilic, Marianna Vitaloni, Manel Esteller^*, Juan Carlos Izpisua Belmonte

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network.

Original language	English (US)
Pages (from-to)	1696-1702
Number of pages	7
Journal	STEM CELLS
Volume	30
Issue number	8
DOIs	https://doi.org/10.1002/stem.1138
State	Published - Aug 2012
Externally published	Yes

Keywords

DNA methylation
Epigenetics
Gene expression
Induced pluripotent stem cells
Pluripotent stem cells
Reprogramming

ASJC Scopus subject areas

General Medicine

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10.1002/stem.1138

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title = "DNA hypermethylation in somatic cells correlates with higher reprogramming efficiency",

abstract = "The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network.",

keywords = "DNA methylation, Epigenetics, Gene expression, Induced pluripotent stem cells, Pluripotent stem cells, Reprogramming",

author = "Barrero, {Mar{\'i}a J.} and Mar{\'i}a Berdasco and Ida Paramonov and Josipa Bilic and Marianna Vitaloni and Manel Esteller and Belmonte, {Juan Carlos Izpisua}",

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AU - Barrero, María J.

AU - Berdasco, María

AU - Paramonov, Ida

AU - Bilic, Josipa

AU - Vitaloni, Marianna

AU - Esteller, Manel

AU - Belmonte, Juan Carlos Izpisua

PY - 2012/8

Y1 - 2012/8

N2 - The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network.

AB - The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network.

KW - DNA methylation

KW - Epigenetics

KW - Gene expression

KW - Induced pluripotent stem cells

KW - Pluripotent stem cells

KW - Reprogramming

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DNA hypermethylation in somatic cells correlates with higher reprogramming efficiency

Abstract

Keywords

ASJC Scopus subject areas

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