TY - JOUR

T1 - Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts

AU - Matveeva, Natalia M.

AU - Fishman, Veniamin S.

AU - Zakharova, Irina S.

AU - Shevchenko, Alexander I.

AU - Pristyazhnyuk, Inna E.

AU - Menzorov, Aleksei G.

AU - Serov, Oleg L.

N1 - Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/22

Y1 - 2017/12/22

N2 - For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34-43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25-29% of these genes display intermediate levels of expression, and 12-16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.

AB - For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34-43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25-29% of these genes display intermediate levels of expression, and 12-16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.

KW - Animals

KW - Cell Differentiation

KW - Cell Fusion

KW - Fibroblasts/cytology

KW - Gene Expression Profiling

KW - Genome

KW - Hybrid Cells/cytology

KW - Mice

KW - Mouse Embryonic Stem Cells/cytology

KW - SOMATIC-CELLS

KW - STAGE

KW - STATE

KW - HYBRIDIZATION

KW - PLURIPOTENCY

KW - CHROMOSOMES

KW - CHOICE

KW - IN-VITRO

KW - EXPRESSION

KW - CYCLE

UR - http://www.scopus.com/inward/record.url?scp=85039164162&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-18352-4

DO - 10.1038/s41598-017-18352-4

M3 - Article

C2 - 29273752

AN - SCOPUS:85039164162

VL - 7

SP - 18094

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 18094

ER -