File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Recent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy

TitleRecent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy
Authors
KeywordsCardiovascular diseases
Lamin A/C
Stem cell model
Transgenic mice model
Issue Date2016
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com
Citation
Stem Cell Research & Therapy, 2016, v. 7, article no. 139 How to Cite?
AbstractLaminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.
Persistent Identifierhttp://hdl.handle.net/10722/232048
ISSN
2018 Impact Factor: 4.627
2015 SCImago Journal Rankings: 1.405
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, YK-
dc.contributor.authorJiang, Y-
dc.contributor.authorRan, X-
dc.contributor.authorLau, YM-
dc.contributor.authorNg, KM-
dc.contributor.authorLai, KWH-
dc.contributor.authorSiu, CW-
dc.contributor.authorTse, HF-
dc.date.accessioned2016-09-20T05:27:20Z-
dc.date.available2016-09-20T05:27:20Z-
dc.date.issued2016-
dc.identifier.citationStem Cell Research & Therapy, 2016, v. 7, article no. 139-
dc.identifier.issn1757-6512-
dc.identifier.urihttp://hdl.handle.net/10722/232048-
dc.description.abstractLaminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com-
dc.relation.ispartofStem Cell Research & Therapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCardiovascular diseases-
dc.subjectLamin A/C-
dc.subjectStem cell model-
dc.subjectTransgenic mice model-
dc.titleRecent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy-
dc.typeArticle-
dc.identifier.emailLee, YK: carol801@hku.hk-
dc.identifier.emailJiang, Y: warm@hku.hk-
dc.identifier.emailLau, YM: vymlau@hku.hk-
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hk-
dc.identifier.emailLai, KWH: kwhlai@hku.hk-
dc.identifier.emailSiu, CW: cwdsiu@hkucc.hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.authorityLee, YK=rp02636-
dc.identifier.authorityNg, KM=rp01670-
dc.identifier.authoritySiu, CW=rp00534-
dc.identifier.authorityTse, HF=rp00428-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13287-016-0401-5-
dc.identifier.pmid27649756-
dc.identifier.pmcidPMC5029055-
dc.identifier.scopuseid_2-s2.0-84988557278-
dc.identifier.hkuros265432-
dc.identifier.volume7-
dc.identifier.spagearticle no. 139-
dc.identifier.epagearticle no. 139-
dc.identifier.isiWOS:000384598600005-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats