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

TitleModeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes
Authors
Issue Date2012
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2012, v. 21 n. 1, p. 32-45 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/134442
ISSN
2014 Impact Factor: 6.393
2014 SCImago Journal Rankings: 3.760
ISI Accession Number ID
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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLi, Wen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorFan, Wen_HK
dc.contributor.authorZhao, Pen_HK
dc.contributor.authorChan, YCen_HK
dc.contributor.authorChen, Sen_HK
dc.contributor.authorZhang, Sen_HK
dc.contributor.authorGuo, Xen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorCai, Jen_HK
dc.contributor.authorQin, Den_HK
dc.contributor.authorLi, Xen_HK
dc.contributor.authorYang, Jen_HK
dc.contributor.authorPeng, Ten_HK
dc.contributor.authorZychlinski, Den_HK
dc.contributor.authorHoffmann, Den_HK
dc.contributor.authorZhang, Ren_HK
dc.contributor.authorDeng, Ken_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorMenten, Ben_HK
dc.contributor.authorZhong, Men_HK
dc.contributor.authorWu, Jen_HK
dc.contributor.authorLi, Zen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorSchambach, Aen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorPei, Den_HK
dc.contributor.authorEsteban, MAen_HK
dc.date.accessioned2011-06-17T09:20:41Z-
dc.date.available2011-06-17T09:20:41Z-
dc.date.issued2012en_HK
dc.identifier.citationHuman Molecular Genetics, 2012, v. 21 n. 1, p. 32-45en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134442-
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.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
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 syndromesen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, YC: ycchan09@hku.hken_HK
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityNg, KM=rp01670en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/hmg/ddr435en_HK
dc.identifier.pmid21949351-
dc.identifier.scopuseid_2-s2.0-83455213526en_HK
dc.identifier.hkuros185841en_US
dc.identifier.hkuros203426-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-83455213526&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue1en_HK
dc.identifier.spage32en_HK
dc.identifier.epage45en_HK
dc.identifier.isiWOS:000297865100004-
dc.publisher.placeUnited Kingdomen_HK
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.identifier.scopusauthoridLi, W=36068145000en_HK
dc.identifier.scopusauthoridWang, X=37032149600en_HK
dc.identifier.scopusauthoridFan, W=54683781400en_HK
dc.identifier.scopusauthoridZhao, P=7202024112en_HK
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridChen, S=51161034100en_HK
dc.identifier.scopusauthoridZhang, S=54685552500en_HK
dc.identifier.scopusauthoridGuo, X=36463626600en_HK
dc.identifier.scopusauthoridZhang, Y=37032325900en_HK
dc.identifier.scopusauthoridLi, Y=51161428400en_HK
dc.identifier.scopusauthoridCai, J=9246458800en_HK
dc.identifier.scopusauthoridQin, D=23005734400en_HK
dc.identifier.scopusauthoridLi, X=51161444600en_HK
dc.identifier.scopusauthoridYang, J=14026282100en_HK
dc.identifier.scopusauthoridPeng, T=54684893700en_HK
dc.identifier.scopusauthoridZychlinski, D=15758449100en_HK
dc.identifier.scopusauthoridHoffmann, D=24546541500en_HK
dc.identifier.scopusauthoridZhang, R=52165122400en_HK
dc.identifier.scopusauthoridDeng, K=35278069800en_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridMenten, B=6505972689en_HK
dc.identifier.scopusauthoridZhong, M=7102458860en_HK
dc.identifier.scopusauthoridWu, J=38062450100en_HK
dc.identifier.scopusauthoridLi, Z=54684364100en_HK
dc.identifier.scopusauthoridChen, Y=7601445337en_HK
dc.identifier.scopusauthoridSchambach, A=6507714915en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridPei, D=7102806599en_HK
dc.identifier.scopusauthoridEsteban, MA=35591774300en_HK

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