Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes

Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes

There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the “fetal” TNNI gene, TNNI1 (ssTnI), together in temporal con...

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Main Authors: Bedada, Fikru B., Chan, Sunny S-K., Metzger, Stefania K., Zhang, Liying, Zhang, Jianyi, Garry, Daniel J., Kamp, Timothy J., Kyba, Michael, Metzger, Joseph M.
Format: Online
Language:English
Published: Elsevier 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223713/
id pubmed-4223713
recordtype oai_dc
spelling pubmed-42237132014-11-09 Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes Bedada, Fikru B. Chan, Sunny S-K. Metzger, Stefania K. Zhang, Liying Zhang, Jianyi Garry, Daniel J. Kamp, Timothy J. Kyba, Michael Metzger, Joseph M. Article There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the “fetal” TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories. Elsevier 2014-09-04 /pmc/articles/PMC4223713/ /pubmed/25358788 http://dx.doi.org/10.1016/j.stemcr.2014.07.012 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bedada, Fikru B.
Chan, Sunny S-K.
Metzger, Stefania K.
Zhang, Liying
Zhang, Jianyi
Garry, Daniel J.
Kamp, Timothy J.
Kyba, Michael
Metzger, Joseph M.
spellingShingle Bedada, Fikru B.
Chan, Sunny S-K.
Metzger, Stefania K.
Zhang, Liying
Zhang, Jianyi
Garry, Daniel J.
Kamp, Timothy J.
Kyba, Michael
Metzger, Joseph M.
Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
author_facet Bedada, Fikru B.
Chan, Sunny S-K.
Metzger, Stefania K.
Zhang, Liying
Zhang, Jianyi
Garry, Daniel J.
Kamp, Timothy J.
Kyba, Michael
Metzger, Joseph M.
author_sort Bedada, Fikru B.
title Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
title_short Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
title_full Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
title_fullStr Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
title_full_unstemmed Acquisition of a Quantitative, Stoichiometrically Conserved Ratiometric Marker of Maturation Status in Stem Cell-Derived Cardiac Myocytes
title_sort acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes
description There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the “fetal” TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories.
publisher Elsevier
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223713/
_version_ 1613153556440809472

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