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Donor's genome impacts iPS cell outcomes

Induced pluripotent stem cells [iPS cells] made from different body cells are equally capable of being reprogrammed — no matter what organ cells they originated from. But, the genotype of a donor does affect their differentiation behavior, according to a recent study from Finland.

Under laboratory conditions, iPS cells can be made from human cells from varying organ systems. They can be cultivated in unlimited amounts and when needed, be made into cell types such as heart, liver or nerve cells.

Published in the Stem Cell Reports journal, the results of a recent Finish study disprove the idea that cells have an "epigenetic memory", held over from their cells of origin which might impact their ability to differentiate into any other cell type.

Medical research uses induced pluripotent cells in many different ways — such as in the study of disease mechanisms and in drug screenings. They are perfect for biobanking as they can easily be derived from fibroblast cells cultivated from a piece of skin, or grown directly from blood cells. Blood cells are the most useful biobank material as taking a blood sample is simple and done frequently.

However, there were some who questioned whether iPS cells derived from different cell types are fully equal, or whether their differentiation could be influenced by the variety of tissue types the cells were derived from.

To settle the matter, researchers from the University of Helsinki compared characteristics of iPS cells made from skin to those made from blood. Using a comprehensive range of analytic methods, researchers examined DNA methylation in stem cells. Their focus being whether human iPS cells had an "epigenetic memory."

Research results were unambiguous: several different indicators proved that the type of original cell made no difference to a stem cell being fully reprogrammed.

According to Professor Timo Otonkoski from the University of Helsinki: "It is obvious that pluripotent stem cells derived from different cell types are fully equal. These results are highly significant to biobanks ... and previously stored living cell samples remain useful for iPS cell production."

What was surprising was how different iPS cells derived from different individuals became. The genotype of the donor shaped the differentiation behaviour of stem cells much more obviously.

"Genetically determined individual differences in stem cell populations were surprisingly extensive. Functional genotypes related to an illness will require that bio-banks select a large variety of samples from several donors," said Timo Otonkoski PhD, Professor of Molecular Neurology at the Biomedicum Stem Cell Centre in the University of Helsinki in Finland

Abstract Highlights
•Isogenic iPSC from fibroblasts and blood have similar differentiation propensities
•Donor-dependent variability affects molecular and differentiation propensities of iPSCs
•Impact of donor variability exceeds source-cell-specific differences in iPSC lines
•Bona fide iPSC lines from different tissues can be combined in the repositories

Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).



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Jan 27, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   

Somatic cells are cells from any body tissue. Research EXCLUDES the sperm and egg sex cells.
Although induced pluripotent stem cells [iPS cells] can be made from somatic cells, a donor's
genectic makeup was found to affect iPSC outcome.
Image Credit:Otonkoski Lab, University of Helsinki




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