title: Trisomy 12 in HESC leads to no selective in vivo growth advantage in teratomas, but induces an increased abundance of renal development.
abstract: The aim of this investigation was to examine the impact of chromosome 12 amplification (tri-12 cells) in human embryonic stem cells (HESC), following in vivo engraftment to an immunodeficient xeno-model. For this we used sublines from the HESC line HS181, spontaneously exhibiting either low or high frequencies of tri-12 cells. Fluorescent in situ hybridization (FISH) analysis revealed a random distribution of tri-12 cells in the HS181 colonies in vitro. Similarly, the contribution of tri-12 cells to the development of various tissues in teratomas in vivo seemed to be fully random with no particular preference regarding in vivo differentiation pathway of tri-12 HS181 cells compared to HS181 cells with disomy 12 (di-12 cells). On the other hand, following in vivo transplantation the ratio of tri-12/di-12 cells was significantly reduced (P < 0.001), indicating a negative selection for this trisomy in vivo. Moreover, injection of HS181 cultures containing tri-12 cells resulted in a significantly increased abundance of areas compatible with renal formation (P < 0.001), relative teratomas derived from injection of di-12 HS181 cells. However, such areas included no increased relative frequency of tri-12 cells, suggesting indirect mechanism(s) for the increased abundance of renal development. The reasons for such developmental bias are unknown and warrant further investigation.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Gertow
authors.forename: Jessica
authors.initials: J
authors.lastname: Cedervall
authors.forename: Christian
authors.initials: C
authors.lastname: Unger
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szöke
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
authors.forename: Marta P
authors.initials: MP
authors.lastname: Imreh
authors.forename: Lars
authors.initials: L
authors.lastname: Ahrlund-Richter
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004171:Diploidy; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D038081:Organogenesis / Q000235:genetics; D033581:Stem Cell Transplantation; D013724:Teratoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014183:Transplantation, Heterologous; D014314:Trisomy