Trisomy 12 in HESC leads to no selective in vivo growth advantage in teratomas, but induces an increased abundance of renal development.
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.
Gertow
Karin
K
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Cedervall
Jessica
J
Unger
Christian
C
Szöke
Krisztina
K
Blennow
Elisabeth
E
Imreh
Marta P
MP
Ahrlund-Richter
Lars
L
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