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Article: Structural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes

TitleStructural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes
Authors
Keywordsapoptosis
calcium cell level
calcium signaling
calcium transport
cardiac muscle cell
Issue Date2019
PublisherHindawi Publishing Corporation. The Journal's web site is located at http://www.sage-hindawi.com/journals/sci/
Citation
Stem Cells International, 2019, v. 2019, p. article no. 8765752 How to Cite?
AbstractThe loss of nonregenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is generally considered irreversible. Human pluripotent stem cells (hPSCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including ventricular (V) cardiomyocytes (CMs), to provide a potential unlimited ex vivo source of CMs for heart disease modeling, drug/cardiotoxicity screening, and cell-based therapies. In the human heart, cytosolic Ca2+ signals are well characterized but the contribution of nuclear Ca2+ is essentially unexplored. The present study investigated nuclear Ca2+ signaling in hPSC-VCMs. Calcium transient or sparks in hPSC-VCMs were measured by line scanning using a spinning disc confocal microscope. We observed that nuclear Ca2+, which stems from unitary sparks due to the diffusion of cytosolic Ca2+ that are mediated by RyRs on the nuclear reticulum, is functional. Parvalbumin- (PV-) mediated Ca2+ buffering successfully manipulated Ca2+ transient and stimuli-induced apoptosis in hPSC-VCMs. We also investigated the effect of Ca2+ on gene transcription in hPSC-VCMs, and the involvement of nuclear factor of activated T-cell (NFAT) pathway was identified. The overexpression of Ca2+-sensitive, nuclear localized Ca2+/calmodulin-dependent protein kinase II δB (CaMKIIδB) induced cardiac hypertrophy through nuclear Ca2+/CaMKIIδB/HDAC4/MEF2 pathway. These findings provide insights into nuclear Ca2+ signal in hPSC-VCMs, which may lead to novel strategies for maturation as well as improved systems for disease modeling, drug discovery, and cell-based therapies.
Persistent Identifierhttp://hdl.handle.net/10722/277183
ISSN
2023 Impact Factor: 3.8
2023 SCImago Journal Rankings: 0.844
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, S-
dc.contributor.authorKeung, W-
dc.contributor.authorCheng, H-
dc.contributor.authorLi, RA-
dc.date.accessioned2019-09-20T08:46:12Z-
dc.date.available2019-09-20T08:46:12Z-
dc.date.issued2019-
dc.identifier.citationStem Cells International, 2019, v. 2019, p. article no. 8765752-
dc.identifier.issn1687-966X-
dc.identifier.urihttp://hdl.handle.net/10722/277183-
dc.description.abstractThe loss of nonregenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is generally considered irreversible. Human pluripotent stem cells (hPSCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including ventricular (V) cardiomyocytes (CMs), to provide a potential unlimited ex vivo source of CMs for heart disease modeling, drug/cardiotoxicity screening, and cell-based therapies. In the human heart, cytosolic Ca2+ signals are well characterized but the contribution of nuclear Ca2+ is essentially unexplored. The present study investigated nuclear Ca2+ signaling in hPSC-VCMs. Calcium transient or sparks in hPSC-VCMs were measured by line scanning using a spinning disc confocal microscope. We observed that nuclear Ca2+, which stems from unitary sparks due to the diffusion of cytosolic Ca2+ that are mediated by RyRs on the nuclear reticulum, is functional. Parvalbumin- (PV-) mediated Ca2+ buffering successfully manipulated Ca2+ transient and stimuli-induced apoptosis in hPSC-VCMs. We also investigated the effect of Ca2+ on gene transcription in hPSC-VCMs, and the involvement of nuclear factor of activated T-cell (NFAT) pathway was identified. The overexpression of Ca2+-sensitive, nuclear localized Ca2+/calmodulin-dependent protein kinase II δB (CaMKIIδB) induced cardiac hypertrophy through nuclear Ca2+/CaMKIIδB/HDAC4/MEF2 pathway. These findings provide insights into nuclear Ca2+ signal in hPSC-VCMs, which may lead to novel strategies for maturation as well as improved systems for disease modeling, drug discovery, and cell-based therapies.-
dc.languageeng-
dc.publisherHindawi Publishing Corporation. The Journal's web site is located at http://www.sage-hindawi.com/journals/sci/-
dc.relation.ispartofStem Cells International-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectapoptosis-
dc.subjectcalcium cell level-
dc.subjectcalcium signaling-
dc.subjectcalcium transport-
dc.subjectcardiac muscle cell-
dc.titleStructural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes-
dc.typeArticle-
dc.identifier.emailKeung, W: wkeung@hku.hk-
dc.identifier.emailLi, RA: ronaldli@hkucc.hku.hk-
dc.identifier.authorityKeung, W=rp01887-
dc.identifier.authorityLi, RA=rp01352-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2019/8765752-
dc.identifier.pmid31065282-
dc.identifier.pmcidPMC6466844-
dc.identifier.scopuseid_2-s2.0-85065831924-
dc.identifier.hkuros305872-
dc.identifier.volume2019-
dc.identifier.spagearticle no. 8765752-
dc.identifier.epagearticle no. 8765752-
dc.identifier.isiWOS:000464824400001-
dc.publisher.placeUnited States-
dc.identifier.issnl1687-966X-

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