中科院广州生物医药与健康研究院裴端卿博士和Miguel Esteban博士研究组成员成功建立了特纳氏综合症、Warkany综合症、13三体综合症和Emanuel综合症的诱导性多能干细胞，并证明了染色体非整倍体不影响重编程的发生和完成，不影响多能性细胞的自我更新和分化能力。
此外，研究人员对特纳氏综合症的IPSCs进行了非整倍体对胚胎早期发育影响的深入探索，发现在特纳氏综合症的诱导性多能干细胞的早期发育过程中，与胎盘相关的基因CSF2RA的表达水平较正常的多能性细胞低。
该项研究指出，关键基因表达剂量的减少可能导致特纳综合症的胚胎的胎盘发育不全，最终引发流产。该成果近期已发表在国际学术期刊Human Molecular Genetics。
非整倍体是指整倍染色体中缺少或额外多出一条或若干条染色体。非整倍体胚胎在早期发育过程中约有2/3会自发流产，存活到出生后的新生儿一般都有严重的由于器官发育畸形而导致的生理疾病和智力障碍，严重的在出生后一年内死亡。目前关于染色体非整倍体综合症的发病机理不明，由于材料难以获得，相关研究进展缓慢。
该项研究建立的非整倍体诱导性多能干细胞为进一步研究其他非整倍体胚胎早期发育过程中出现的问题提供了干细胞来源。(生物谷：Bioon.com)
doi:10.1093/hmg/ddr435
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Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
Wen Li1,†, Xianming Wang1,2,†, Wenxia Fan1,†, Ping Zhao1, Yau-Chi Chan3, Shen Chen1, Shiqiang Zhang1, Xiangpeng Guo1, Ya Zhang1, Yanhua Li et al.
Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.
