title: Transformation of somatic cells into stem cell-like cells under a stromal niche.
abstract: To study the genomic plasticity of somatic cells without ectopic genetic manipulation, we cultured mouse fibroblasts with ovarian cells, embryonic fibroblasts of different strains, and parthenogenetic embryonic stem cells (ESCs). Of 41 trials, cell aggregation resembling nascent ESC colony from inner cell mass was detected in 9 cases (22%), and 6 cases (67%) yielded fibroblast-derived colonies with ESC morphology. Cells used in coculture provided the critical (P=0.0061) inducing factor for the aggregation. These colony-forming fibroblasts (CFFs) showed similar characteristics to those in ESCs and induced pluripotent stem cells (iPSCs), including pluripotency gene expression, in vitro differentiation, and teratoma formation. Furthermore, CFFs produced somatic chimera, although none showed germline chimerism. CFFs had a tetraploid-like karyotype, and their imprinting patterns differed from parthenogenetic ESCs, thereby confirming their nongermline transmissibility. We observed dysregulation of cell cycle-related proteins, as well as both homologous and heterologous recombination of genomic single-nucleotide polymorphisms in CFFs. Our observations provide information on somatic cell plasticity, resulting in stemness or tumorigenesis, regardless of colony-forming cell progenitors in the fibroblast population. The plasticity of somatic genomes under environmental influences, as well as acquisition of pluripotency by cell fusion, is also implicated.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Seung Pyo
authors.initials: SP
authors.lastname: Gong
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Yum
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Chae Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Choi
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Hojae
authors.initials: H
authors.lastname: Han
authors.forename: Kye-Seong
authors.initials: KS
authors.lastname: Kim
authors.forename: Eriona
authors.initials: E
authors.lastname: Hysolli
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Ahn
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Han
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Jeong Mook
authors.initials: JM
authors.lastname: Lim
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D054337:Cell Dedifferentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D020869:Gene Expression Profiling; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007621:Karyotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary / Q000166:cytology; D013045:Species Specificity; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure
keywords: colony-forming fibroblasts; genetic and cellular plasticity; microenvironment; pluripotency; reprogramming