Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming.
Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming.
复制标题
DOI：
10.1038/s41598-021-83399-3
复制
发表时间：
2021-02-22
影响因子：
4.6
通讯作者：
Lebedev IN
中科院分区：
文献类型：
--
作者：
Nikitina TV;Kashevarova AA;Gridina MM;Lopatkina ME;Khabarova AA;Yakovleva YS;Menzorov AG;Minina YA;Pristyazhnyuk IE;Vasilyev SA;Fedotov DA;Serov OL;Lebedev IN
人类环染色体在有丝分裂过程中通常不稳定，子细胞可能部分或完全非整倍体。我们通过 GTG 核型分析和 aCGH 研究了长期培养的皮肤成纤维细胞和诱导多能干细胞 (iPSC) 中 8、13、18 和 22 号四环染色体的有丝分裂稳定性。除 r(18) 外，在所有成纤维细胞培养物中均观察到环染色体丢失和二次畸变。我们发现了索引染色体的单体性、片段化和易位。在 iPSC 中，aCGH 揭示了具有不同环的 iPSC 系之间以及在某些情况下具有相同环染色体的细胞系之间有丝分裂稳定性的显着差异。我们通过环染色体丢失和 isoUPD(8)pat 发生的完整同源复制，在所有六个 iPSC 系中记录了核型 46,XY,r(8) 至 46,XY 的自发拯救，如 SNP 基因型分布分析所证明的那样。在具有其他环染色体的 iPSC 中，未观察到核型校正。我们的结果表明，iPSC 中环染色体核型的自发校正并不普遍，并且多能性与多种衍生核型兼容。我们得出的结论是，成纤维细胞和 iPSC 培养物中二次重排频率存在显着变异，扩大了构成环染色体的临床意义。
Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome.
登录
查看更多内容
影响因子：
--
作者：
Burgess, Trent;Downie, Lilian;Pszczola, Rosalynn
通讯作者：
Pszczola, Rosalynn
影响因子：
5.9
作者：
Baker, Duncan;Hirst, Adam J.;Gokhale, Paul J.;Juarez, Miguel A.;Williams, Steve;Wheeler, Mark;Bean, Kerry;Allison, Thomas F.;Moore, Harry D.;Andrews, Peter W.;Barbaric, Ivana
通讯作者：
Barbaric, Ivana
影响因子：
46.9
作者：
Blum, Barak;Bar-Nur, Ori;Benvenisty, Nissim
通讯作者：
Benvenisty, Nissim
影响因子：
1.9
作者：
Gradek, Gyri Aasland;Kvistad, Per Helge;Houge, Gunnar
通讯作者：
Houge, Gunnar
影响因子：
3.2
作者：
Carreira, Isabel M.;Mascarenhas, Alexandra;Liehr, Thomas
通讯作者：
Liehr, Thomas