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Article: Recent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy
Title | Recent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy |
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Authors | |
Keywords | Cardiovascular diseases Lamin A/C Stem cell model Transgenic mice model |
Issue Date | 2016 |
Publisher | BioMed 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? |
Abstract | Laminopathy 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 Identifier | http://hdl.handle.net/10722/232048 |
ISSN | 2023 Impact Factor: 7.1 2023 SCImago Journal Rankings: 1.798 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lee, YK | - |
dc.contributor.author | Jiang, Y | - |
dc.contributor.author | Ran, X | - |
dc.contributor.author | Lau, YM | - |
dc.contributor.author | Ng, KM | - |
dc.contributor.author | Lai, KWH | - |
dc.contributor.author | Siu, CW | - |
dc.contributor.author | Tse, HF | - |
dc.date.accessioned | 2016-09-20T05:27:20Z | - |
dc.date.available | 2016-09-20T05:27:20Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Stem Cell Research & Therapy, 2016, v. 7, article no. 139 | - |
dc.identifier.issn | 1757-6512 | - |
dc.identifier.uri | http://hdl.handle.net/10722/232048 | - |
dc.description.abstract | Laminopathy 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.language | eng | - |
dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com | - |
dc.relation.ispartof | Stem Cell Research & Therapy | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Cardiovascular diseases | - |
dc.subject | Lamin A/C | - |
dc.subject | Stem cell model | - |
dc.subject | Transgenic mice model | - |
dc.title | Recent Advances in Animal and Human Pluripotent Stem Cell Modeling of Cardiac Laminopathy | - |
dc.type | Article | - |
dc.identifier.email | Lee, YK: carol801@hku.hk | - |
dc.identifier.email | Jiang, Y: warm@hku.hk | - |
dc.identifier.email | Lau, YM: vymlau@hku.hk | - |
dc.identifier.email | Ng, KM: skykmng@hkucc.hku.hk | - |
dc.identifier.email | Lai, KWH: kwhlai@hku.hk | - |
dc.identifier.email | Siu, CW: cwdsiu@hkucc.hku.hk | - |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | - |
dc.identifier.authority | Lee, YK=rp02636 | - |
dc.identifier.authority | Ng, KM=rp01670 | - |
dc.identifier.authority | Siu, CW=rp00534 | - |
dc.identifier.authority | Tse, HF=rp00428 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1186/s13287-016-0401-5 | - |
dc.identifier.pmid | 27649756 | - |
dc.identifier.pmcid | PMC5029055 | - |
dc.identifier.scopus | eid_2-s2.0-84988557278 | - |
dc.identifier.hkuros | 265432 | - |
dc.identifier.volume | 7 | - |
dc.identifier.spage | article no. 139 | - |
dc.identifier.epage | article no. 139 | - |
dc.identifier.isi | WOS:000384598600005 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1757-6512 | - |