A proliferative burst during preadolescence establishes the final cardiomyocyte number

Nawazish Naqvi; Ming Li; John W. Calvert; Thor Tejada; Jonathan P. Lambert; Jianxin Wu; Scott H. Kesteven; Sara R. Holman; Torahiro Matsuda; Joshua D. Lovelock; Wesley W. Howard; Siiri E. Iismaa; Andrea Y. Chan; Brian H. Crawford; Mary B. Wagner; David I. K. Martin; David J. Lefer; Robert M. Graham; Ahsan Husain

doi:10.1016/j.cell.2014.03.035

A proliferative burst during preadolescence establishes the final cardiomyocyte number

Nawazish Naqvi, Ming Li, John W. Calvert, Thor Tejada, Jonathan P. Lambert, Jianxin Wu, Scott H. Kesteven, Sara R. Holman, Torahiro Matsuda, Joshua D. Lovelock, Wesley W. Howard, Siiri E. Iismaa, Andrea Y. Chan, Brian H. Crawford, Mary B. Wagner, David I. K. Martin, David J. Lefer, Robert M. Graham, Ahsan Husain

Research output: Contribution to journal › Article › peer-review

195 Citations (Scopus)

Abstract

It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

Original language	English
Pages (from-to)	795-807
Number of pages	13
Journal	Cell
Volume	157
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2014.03.035
Publication status	Published - 8 May 2014
Externally published	Yes

Keywords

Animals
Cell Differentiation
Cell Proliferation
Cell Separation
Heart/growth & development
Male
Mice
Mice, Inbred C57BL
Myocytes, Cardiac/cytology
Triiodothyronine/metabolism

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10.1016/j.cell.2014.03.035

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Naqvi, N., Li, M., Calvert, J. W., Tejada, T., Lambert, J. P., Wu, J., Kesteven, S. H., Holman, S. R., Matsuda, T., Lovelock, J. D., Howard, W. W., Iismaa, S. E., Chan, A. Y., Crawford, B. H., Wagner, M. B., Martin, D. I. K., Lefer, D. J., Graham, R. M., & Husain, A. (2014). A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell, 157(4), 795-807. https://doi.org/10.1016/j.cell.2014.03.035

Naqvi, Nawazish ; Li, Ming ; Calvert, John W. ; Tejada, Thor ; Lambert, Jonathan P. ; Wu, Jianxin ; Kesteven, Scott H. ; Holman, Sara R. ; Matsuda, Torahiro ; Lovelock, Joshua D. ; Howard, Wesley W. ; Iismaa, Siiri E. ; Chan, Andrea Y. ; Crawford, Brian H. ; Wagner, Mary B. ; Martin, David I. K. ; Lefer, David J. ; Graham, Robert M. ; Husain, Ahsan. / A proliferative burst during preadolescence establishes the final cardiomyocyte number. In: Cell. 2014 ; Vol. 157, No. 4. pp. 795-807.

@article{2e91cfdc57734583ad1789f95a964411,

title = "A proliferative burst during preadolescence establishes the final cardiomyocyte number",

abstract = "It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.",

keywords = "Animals, Cell Differentiation, Cell Proliferation, Cell Separation, Heart/growth & development, Male, Mice, Mice, Inbred C57BL, Myocytes, Cardiac/cytology, Triiodothyronine/metabolism",

author = "Nawazish Naqvi and Ming Li and Calvert, {John W.} and Thor Tejada and Lambert, {Jonathan P.} and Jianxin Wu and Kesteven, {Scott H.} and Holman, {Sara R.} and Torahiro Matsuda and Lovelock, {Joshua D.} and Howard, {Wesley W.} and Iismaa, {Siiri E.} and Chan, {Andrea Y.} and Crawford, {Brian H.} and Wagner, {Mary B.} and Martin, {David I. K.} and Lefer, {David J.} and Graham, {Robert M.} and Ahsan Husain",

year = "2014",

month = may,

day = "8",

doi = "10.1016/j.cell.2014.03.035",

language = "English",

volume = "157",

pages = "795--807",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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Naqvi, N, Li, M, Calvert, JW, Tejada, T, Lambert, JP, Wu, J, Kesteven, SH, Holman, SR, Matsuda, T, Lovelock, JD, Howard, WW, Iismaa, SE, Chan, AY, Crawford, BH, Wagner, MB, Martin, DIK, Lefer, DJ, Graham, RM & Husain, A 2014, 'A proliferative burst during preadolescence establishes the final cardiomyocyte number', Cell, vol. 157, no. 4, pp. 795-807. https://doi.org/10.1016/j.cell.2014.03.035

A proliferative burst during preadolescence establishes the final cardiomyocyte number. / Naqvi, Nawazish; Li, Ming; Calvert, John W.; Tejada, Thor; Lambert, Jonathan P.; Wu, Jianxin; Kesteven, Scott H.; Holman, Sara R.; Matsuda, Torahiro; Lovelock, Joshua D.; Howard, Wesley W.; Iismaa, Siiri E.; Chan, Andrea Y.; Crawford, Brian H.; Wagner, Mary B.; Martin, David I. K.; Lefer, David J.; Graham, Robert M.; Husain, Ahsan.

In: Cell, Vol. 157, No. 4, 08.05.2014, p. 795-807.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A proliferative burst during preadolescence establishes the final cardiomyocyte number

AU - Naqvi, Nawazish

AU - Li, Ming

AU - Calvert, John W.

AU - Tejada, Thor

AU - Lambert, Jonathan P.

AU - Wu, Jianxin

AU - Kesteven, Scott H.

AU - Holman, Sara R.

AU - Matsuda, Torahiro

AU - Lovelock, Joshua D.

AU - Howard, Wesley W.

AU - Iismaa, Siiri E.

AU - Chan, Andrea Y.

AU - Crawford, Brian H.

AU - Wagner, Mary B.

AU - Martin, David I. K.

AU - Lefer, David J.

AU - Graham, Robert M.

AU - Husain, Ahsan

PY - 2014/5/8

Y1 - 2014/5/8

N2 - It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

AB - It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

KW - Animals

KW - Cell Differentiation

KW - Cell Proliferation

KW - Cell Separation

KW - Heart/growth & development

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocytes, Cardiac/cytology

KW - Triiodothyronine/metabolism

UR - http://www.scopus.com/inward/record.url?scp=84900331122&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2014.03.035

DO - 10.1016/j.cell.2014.03.035

M3 - Article

C2 - 24813607

VL - 157

SP - 795

EP - 807

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -

A proliferative burst during preadolescence establishes the final cardiomyocyte number

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