Assessment of DNA synthesis in Islet-1⁺ cells in the adult murine heart

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Assessment of DNA synthesis in Islet-1⁺ cells in the adult murine heart. / Weinberger, Florian; Mehrkens, Dennis; Starbatty, Jutta; Nicol, Philipp; Eschenhagen, Thomas.

in: BIOCHEM BIOPH RES CO, Jahrgang 456, Nr. 1, 02.01.2015, S. 294-7.

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@article{ca650d1a68cb417cac1eed2b0ccace44,
title = "Assessment of DNA synthesis in Islet-1⁺ cells in the adult murine heart",
abstract = "RATIONALE: Islet-1 positive (Islet-1(+)) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1(+) cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart.METHODS AND RESULTS: DNA synthesis was analyzed by the incorporation of tritiated thymidine ((3)H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of (3)H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1(+) cells. Whereas Islet(-) non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed.CONCLUSIONS: Islet-1(+) cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.",
keywords = "Animals, Autoradiography, Cell Nucleus, Cell Proliferation, DNA Replication, Heart, Heart Ventricles, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myocardium, Myocytes, Cardiac, Sinoatrial Node, Stem Cells, Thymidine, Transgenes, beta-Galactosidase",
author = "Florian Weinberger and Dennis Mehrkens and Jutta Starbatty and Philipp Nicol and Thomas Eschenhagen",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2015",
month = jan,
day = "2",
doi = "10.1016/j.bbrc.2014.11.074",
language = "English",
volume = "456",
pages = "294--7",
journal = "BIOCHEM BIOPH RES CO",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

RIS

TY - JOUR

T1 - Assessment of DNA synthesis in Islet-1⁺ cells in the adult murine heart

AU - Weinberger, Florian

AU - Mehrkens, Dennis

AU - Starbatty, Jutta

AU - Nicol, Philipp

AU - Eschenhagen, Thomas

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2015/1/2

Y1 - 2015/1/2

N2 - RATIONALE: Islet-1 positive (Islet-1(+)) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1(+) cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart.METHODS AND RESULTS: DNA synthesis was analyzed by the incorporation of tritiated thymidine ((3)H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of (3)H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1(+) cells. Whereas Islet(-) non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed.CONCLUSIONS: Islet-1(+) cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

AB - RATIONALE: Islet-1 positive (Islet-1(+)) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1(+) cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart.METHODS AND RESULTS: DNA synthesis was analyzed by the incorporation of tritiated thymidine ((3)H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of (3)H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1(+) cells. Whereas Islet(-) non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed.CONCLUSIONS: Islet-1(+) cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

KW - Animals

KW - Autoradiography

KW - Cell Nucleus

KW - Cell Proliferation

KW - DNA Replication

KW - Heart

KW - Heart Ventricles

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Myocardium

KW - Myocytes, Cardiac

KW - Sinoatrial Node

KW - Stem Cells

KW - Thymidine

KW - Transgenes

KW - beta-Galactosidase

U2 - 10.1016/j.bbrc.2014.11.074

DO - 10.1016/j.bbrc.2014.11.074

M3 - SCORING: Journal article

C2 - 25450620

VL - 456

SP - 294

EP - 297

JO - BIOCHEM BIOPH RES CO

JF - BIOCHEM BIOPH RES CO

SN - 0006-291X

IS - 1

ER -