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Article: Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
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TitleModeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
 
AuthorsLi, W5
Wang, X5 3
Fan, W5
Zhao, P5
Chan, YC2
Chen, S5
Zhang, S5
Guo, X5
Zhang, Y5
Li, Y5
Cai, J5
Qin, D5
Li, X5
Yang, J5
Peng, T5
Zychlinski, D4
Hoffmann, D4
Zhang, R5
Deng, K1
Ng, KM2
Menten, B6
Zhong, M1
Wu, J5
Li, Z5
Chen, Y5
Schambach, A4
Tse, HF2
Pei, D5
Esteban, MA5
 
Issue Date2012
 
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
CitationHuman Molecular Genetics, 2012, v. 21 n. 1, p. 32-45 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddr435
 
AbstractMany 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 genesASMTLand 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. © The Author 2011. Published by Oxford University Press.
 
ISSN0964-6906
2013 Impact Factor: 6.677
 
DOIhttp://dx.doi.org/10.1093/hmg/ddr435
 
ISI Accession Number IDWOS:000297865100004
Funding AgencyGrant Number
Ministry of Science and Technology of China2011CB965200
Chinese Academy of SciencesXDA0102000
National S&T Major Special Project on Major New Drug Innovation2011ZX09102-010
Bureau of Science and Technology of Guangzhou Municipality2010U1-E00521
German Academic Exchange Service (DAAD)
German Ministry of Research
Ministry of Science and Technology of China
Research Grants Council of Hong KongHKU 8/CRF/09
HKU 780110M
HKU 7811/11M
Funding Information:

This work was supported by grants from the 973 program of Ministry of Science and Technology of China (2011CB965200) to M. A. E., 'Strategic Priority Research Program' of the Chinese Academy of Sciences (XDA0102000), National S&T Major Special Project on Major New Drug Innovation (2011ZX09102-010) to D. P., Bureau of Science and Technology of Guangzhou Municipality (2010U1-E00521) to D. P., a joint German-Chinese grant from the German Academic Exchange Service (DAAD), the German Ministry of Research and the Ministry of Science and Technology of China to D. P. and A. S., and Collaborative Research Fund (HKU 8/CRF/09) and General Research Fund (HKU 780110M, HKU 7811/11M) grants of the Research Grants Council of Hong Kong to H.-F.T.

 
ReferencesReferences in Scopus
 
GrantsAutologous Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Repair in Porcine Ischemic Cardiomyopathy
Pluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases
 
DC FieldValue
dc.contributor.authorLi, W
 
dc.contributor.authorWang, X
 
dc.contributor.authorFan, W
 
dc.contributor.authorZhao, P
 
dc.contributor.authorChan, YC
 
dc.contributor.authorChen, S
 
dc.contributor.authorZhang, S
 
dc.contributor.authorGuo, X
 
dc.contributor.authorZhang, Y
 
dc.contributor.authorLi, Y
 
dc.contributor.authorCai, J
 
dc.contributor.authorQin, D
 
dc.contributor.authorLi, X
 
dc.contributor.authorYang, J
 
dc.contributor.authorPeng, T
 
dc.contributor.authorZychlinski, D
 
dc.contributor.authorHoffmann, D
 
dc.contributor.authorZhang, R
 
dc.contributor.authorDeng, K
 
dc.contributor.authorNg, KM
 
dc.contributor.authorMenten, B
 
dc.contributor.authorZhong, M
 
dc.contributor.authorWu, J
 
dc.contributor.authorLi, Z
 
dc.contributor.authorChen, Y
 
dc.contributor.authorSchambach, A
 
dc.contributor.authorTse, HF
 
dc.contributor.authorPei, D
 
dc.contributor.authorEsteban, MA
 
dc.date.accessioned2011-06-17T09:20:41Z
 
dc.date.available2011-06-17T09:20:41Z
 
dc.date.issued2012
 
dc.description.abstractMany 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 genesASMTLand 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. © The Author 2011. Published by Oxford University Press.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationHuman Molecular Genetics, 2012, v. 21 n. 1, p. 32-45 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddr435
 
dc.identifier.doihttp://dx.doi.org/10.1093/hmg/ddr435
 
dc.identifier.epage45
 
dc.identifier.hkuros185841
 
dc.identifier.hkuros203426
 
dc.identifier.isiWOS:000297865100004
Funding AgencyGrant Number
Ministry of Science and Technology of China2011CB965200
Chinese Academy of SciencesXDA0102000
National S&T Major Special Project on Major New Drug Innovation2011ZX09102-010
Bureau of Science and Technology of Guangzhou Municipality2010U1-E00521
German Academic Exchange Service (DAAD)
German Ministry of Research
Ministry of Science and Technology of China
Research Grants Council of Hong KongHKU 8/CRF/09
HKU 780110M
HKU 7811/11M
Funding Information:

This work was supported by grants from the 973 program of Ministry of Science and Technology of China (2011CB965200) to M. A. E., 'Strategic Priority Research Program' of the Chinese Academy of Sciences (XDA0102000), National S&T Major Special Project on Major New Drug Innovation (2011ZX09102-010) to D. P., Bureau of Science and Technology of Guangzhou Municipality (2010U1-E00521) to D. P., a joint German-Chinese grant from the German Academic Exchange Service (DAAD), the German Ministry of Research and the Ministry of Science and Technology of China to D. P. and A. S., and Collaborative Research Fund (HKU 8/CRF/09) and General Research Fund (HKU 780110M, HKU 7811/11M) grants of the Research Grants Council of Hong Kong to H.-F.T.

 
dc.identifier.issn0964-6906
2013 Impact Factor: 6.677
 
dc.identifier.issue1
 
dc.identifier.pmid21949351
 
dc.identifier.scopuseid_2-s2.0-83455213526
 
dc.identifier.spage32
 
dc.identifier.urihttp://hdl.handle.net/10722/134442
 
dc.identifier.volume21
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHuman Molecular Genetics
 
dc.relation.projectAutologous Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Repair in Porcine Ischemic Cardiomyopathy
 
dc.relation.projectPluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAneuploidy
 
dc.subject.meshCell Differentiation
 
dc.subject.meshChromosome Disorders - genetics - metabolism - physiopathology
 
dc.subject.meshGene Expression
 
dc.subject.meshInduced Pluripotent Stem Cells - cytology - metabolism
 
dc.titleModeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
 
dc.typeArticle
 
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Author Affiliations
  1. Nanfang Hospital
  2. The University of Hong Kong
  3. University of Science and Technology of China
  4. Medizinische Hochschule Hannover (MHH)
  5. Chinese Academy of Sciences
  6. University Hospital of Ghent