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Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes

Wen Li, Xianming Wang, Wenxia Fan, Ping Zhao, Yau-Chi Chan, Shen Chen, Shiqiang Zhang, Xiangpeng Guo, Ya Zhang and Yanhua Li, et al. (2012) HUMAN MOLECULAR GENETICS. 21(1). p.32-45
abstract
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GENERATION, INDUCTION, X-CHROMOSOME, TURNERS-SYNDROME, HEPATOCYTE-LIKE CELLS, HUMAN SOMATIC-CELLS, DISEASE, VECTOR, GENOME
journal title
HUMAN MOLECULAR GENETICS
Hum. Mol. Genet.
volume
21
issue
1
pages
32 - 45
Web of Science type
Article
Web of Science id
000297865100004
JCR category
GENETICS & HEREDITY
JCR impact factor
7.692 (2012)
JCR rank
13/161 (2012)
JCR quartile
1 (2012)
ISSN
0964-6906
DOI
10.1093/hmg/ddr435
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1983820
handle
http://hdl.handle.net/1854/LU-1983820
date created
2012-01-11 16:28:42
date last changed
2012-01-13 14:04:31
@article{1983820,
  abstract     = {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.},
  author       = {Li, Wen and Wang, Xianming and Fan, Wenxia and Zhao, Ping and Chan, Yau-Chi and Chen, Shen and Zhang, Shiqiang and Guo, Xiangpeng and Zhang, Ya and Li, Yanhua and Cai, Jinglei and Qin, Dajiang and Li, Xingyan and Yang, Jiayin and Peng, Tianran and Zychlinski, Daniela and Hoffmann, Dirk and Zhang, Ruosi and Deng, Kang and Ng, Kwong-Man and Menten, Bj{\"o}rn and Zhong, Mei and Wu, Jiayan and Li, Zhiyuan and Chen, Yonglong and Schambach, Axel and Tse, Hung-Fat and Pei, Duanqing and Esteban, Miguel A},
  issn         = {0964-6906},
  journal      = {HUMAN MOLECULAR GENETICS},
  keyword      = {GENERATION,INDUCTION,X-CHROMOSOME,TURNERS-SYNDROME,HEPATOCYTE-LIKE CELLS,HUMAN SOMATIC-CELLS,DISEASE,VECTOR,GENOME},
  language     = {eng},
  number       = {1},
  pages        = {32--45},
  title        = {Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes},
  url          = {http://dx.doi.org/10.1093/hmg/ddr435},
  volume       = {21},
  year         = {2012},
}

Chicago
Li, Wen, Xianming Wang, Wenxia Fan, Ping Zhao, Yau-Chi Chan, Shen Chen, Shiqiang Zhang, et al. 2012. “Modeling Abnormal Early Development with Induced Pluripotent Stem Cells from Aneuploid Syndromes.” Human Molecular Genetics 21 (1): 32–45.
APA
Li, Wen, Wang, X., Fan, W., Zhao, P., Chan, Y.-C., Chen, S., Zhang, S., et al. (2012). Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes. HUMAN MOLECULAR GENETICS, 21(1), 32–45.
Vancouver
1.
Li W, Wang X, Fan W, Zhao P, Chan Y-C, Chen S, et al. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes. HUMAN MOLECULAR GENETICS. 2012;21(1):32–45.
MLA
Li, Wen, Xianming Wang, Wenxia Fan, et al. “Modeling Abnormal Early Development with Induced Pluripotent Stem Cells from Aneuploid Syndromes.” HUMAN MOLECULAR GENETICS 21.1 (2012): 32–45. Print.