| Autor: |
Jeong, Ho-Chang, Go, Young-Hyun, Shin, Joong-Gon, Kim, Yun-Jeong, Cho, Min-Guk, Gwon, Dasom, Cheong, Hyun Sub, Lee, Haeseung, Lee, Jae-Ho, Jang, Chang-Young, Shin, Hyoung Doo, Cha, Hyuk-Jin |
| Předmět: |
|
| Zdroj: |
Stem Cell Reviews & Reports; Jul2023, Vol. 19 Issue 5, p1466-1481, 16p |
| Abstrakt: |
Background: Despite highly effective machinery for the maintenance of genome integrity in human embryonic stem cells (hESCs), the frequency of genetic aberrations during in-vitro culture has been a serious issue for future clinical applications. Method: By passaging hESCs over a broad range of timepoints (up to 6 years), the isogenic hESC lines with different passage numbers with distinct cellular characteristics, were established. Result: We found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs) with normal copy number. Through high-resolution genome-wide approaches and transcriptome analysis, we found that culture adapted-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2, a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stabilization, misaligned chromosomes, and polyploidy. Conclusion: These studies suggest that the increased transcription of TPX2 in culture adapted hESCs could contribute to an increase in aberrant mitosis due to altered spindle dynamics. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
