Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome.
The recent discovery of induced pluripotent stem cell (iPSC) technology provides an invaluable tool for creating in vitro representations of human genetic conditions. This is particularly relevant for those diseases that lack adequate animal models or where the species comparison is difficult, e.g. imprinting diseases such as the neurogenetic disorder Prader-Willi syndrome (PWS). However, recent reports have unveiled transcriptional and functional differences between iPSCs and embryonic stem cells that in cases are attributable to imprinting errors. This has suggested that human iPSCs may not be useful to model genetic imprinting diseases. Here, we describe the generation of iPSCs from a patient with PWS bearing a partial translocation of the paternally expressed chromosome 15q11-q13 region to chromosome 4. The resulting iPSCs match all standard criteria of bona fide reprogramming and could be readily differentiated into tissues derived from the three germ layers, including neurons. Moreover, these iPSCs retain a high level of DNA methylation in the imprinting center of the maternal allele and show concomitant reduced expression of the disease-associated small nucleolar RNA HBII-85/SNORD116. These results indicate that iPSCs may be a useful tool to study PWS and perhaps other genetic imprinting diseases as well.
Yang
Jiayin
J
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Cai
Jie
J
Zhang
Ya
Y
Wang
Xianming
X
Li
Wen
W
Xu
Jianyong
J
Li
Feng
F
Guo
Xiangpeng
X
Deng
Kang
K
Zhong
Mei
M
Chen
Yonglong
Y
Lai
Liangxue
L
Pei
Duanqing
D
Esteban
Miguel A
MA
D054337:Cell Dedifferentiation / Q000235:genetics; D002478:Cells, Cultured; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000378:metabolism; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D018392:Genomic Imprinting; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012342:RNA, Small Nuclear / Q000096:biosynthesis / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
D012342:RNA, Small Nuclear