Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm

Marc C. Engels; Kuppusamy Rajarajan; Rebecca Feistritzer; Arun Sharma; Ulrik B. Nielsen; Martin J. Schalij; Antoine A.F. De Vries; Daniël A. Pijnappels; Sean M. Wu

doi:10.1002/stem.1660

Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm

Marc C. Engels, Kuppusamy Rajarajan, Rebecca Feistritzer, Arun Sharma, Ulrik B. Nielsen, Martin J. Schalij, Antoine A.F. De Vries, Daniël A. Pijnappels, Sean M. Wu

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

27 Scopus citations

Abstract

A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5 ⁺ cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. Stem Cells 2014;32:1493-1502

Original language	English (US)
Pages (from-to)	1493-1502
Number of pages	10
Journal	Stem Cells
Volume	32
Issue number	6
DOIs	https://doi.org/10.1002/stem.1660
State	Published - Jun 2014
Externally published	Yes

Keywords

Akt
Cardiac differentiation
Cardiac progenitor cell
Cardiomyocyte
Development
Embryonic stem cell
In vitro screening
Insulin
Insulin-like growth factor
Mesoderm

ASJC Scopus subject areas

Molecular Medicine
Developmental Biology
Cell Biology

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10.1002/stem.1660

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title = "Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm",

abstract = "A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5 + cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. Stem Cells 2014;32:1493-1502",

keywords = "Akt, Cardiac differentiation, Cardiac progenitor cell, Cardiomyocyte, Development, Embryonic stem cell, In vitro screening, Insulin, Insulin-like growth factor, Mesoderm",

author = "Engels, {Marc C.} and Kuppusamy Rajarajan and Rebecca Feistritzer and Arun Sharma and Nielsen, {Ulrik B.} and Schalij, {Martin J.} and {De Vries}, {Antoine A.F.} and Pijnappels, {Dani{\"e}l A.} and Wu, {Sean M.}",

year = "2014",

month = jun,

doi = "10.1002/stem.1660",

language = "English (US)",

volume = "32",

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AU - Engels, Marc C.

AU - Rajarajan, Kuppusamy

AU - Feistritzer, Rebecca

AU - Sharma, Arun

AU - Nielsen, Ulrik B.

AU - Schalij, Martin J.

AU - De Vries, Antoine A.F.

AU - Pijnappels, Daniël A.

AU - Wu, Sean M.

PY - 2014/6

Y1 - 2014/6

N2 - A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5 + cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. Stem Cells 2014;32:1493-1502

AB - A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5 + cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e.g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. Stem Cells 2014;32:1493-1502

KW - Akt

KW - Cardiac differentiation

KW - Cardiac progenitor cell

KW - Cardiomyocyte

KW - Development

KW - Embryonic stem cell

KW - In vitro screening

KW - Insulin

KW - Insulin-like growth factor

KW - Mesoderm

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Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm

Abstract

Keywords

ASJC Scopus subject areas

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