In vitro culture conditions favoring selection of chromosomal abnormalities in human ES cells
| Autor: | M.P. Imreh, Sirac Dilber, Christian Unger, E. Blennow, L. Csöregh, K. Szöke, Karin Gertow, K. Holmberg, Lars Ährlund-Richter, G. Fried, J. Cedervall |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Genetic Markers
Male Pluripotent Stem Cells Population Transplantation Heterologous Cell Culture Techniques Embryoid body Mice SCID Biology medicine.disease_cause Biochemistry Cell Line Mice Chromosomal Instability medicine Animals Humans Selection Genetic education Molecular Biology In Situ Hybridization Fluorescence DNA Primers Genetics Chromosome Aberrations education.field_of_study Mutation Base Sequence Reverse Transcriptase Polymerase Chain Reaction Cell Biology Embryonic stem cell Cell biology Chromosome Banding Extracellular Matrix Transplantation medicine.anatomical_structure Tumor progression Cell culture Karyotyping embryonic structures Germ cell Stem Cell Transplantation |
| Zdroj: | Journal of cellular biochemistry. 99(2) |
| ISSN: | 0730-2312 |
| Popis: | Previous studies in several laboratories have demonstrated inadvertent chromosomal abnormalities in long-term cultured human embryonic stem cells (HESC). Here, using a two-step selection process we report a functional adaptation of a HESC line, HS181, towards a decreased dependence of extra cellular matrix (ECM) for in vitro survival, that is for growth directly onto a plastic surface. Successful adaptation was paralleled with a karyotype change in 100% of the cells to 47,XX,del(7)(q11.2),+i(12)(p10). The resulting adapted population showed increased survival and growth on plastic and also maintained expression of HESC markers, but showed a decreased pluripotency, as demonstrated by results from embryoid body (EB) formation in vitro. The finding of reduced pluripotency may not be totally unexpected since the variant cells were selected for self-renewal and proliferation, not differentiation during the adaptation to growth on plastic. In the light of recent models of a germ cell origin of HESC it is of particular interest that similar to many of the reported spontaneous HESC mutants, one of the identified specific chromosome abnormalities, i(12p), has also been strongly implicated for human germ cell cancer. However, the mutated HESC variant carrying this mutation failed to grow as a xeno-graft in a mouse model in vivo. This is surprising and needs a further mechanistic analysis for its explanation. Increased knowledge of genetic integrity of HESC may have significance on the understanding of mechanisms for tumor progression and thus strategy for treatments, particularly for tumors occurring in early life. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text