Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells

Medet Jumabay, Jiayinaguli Zhumabai, Nurlan Mansurov, Katharine C Niklason, Pierre J Guihard, Mark R Cubberly, Alan M Fogelman, Luisa Iruela-Arispe, Yucheng Yao, Arman Saparov, Kristina I Boström

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Bone morphogenetic protein (BMP) 10, a cardiac-restricted BMP family member, is essential in cardiomyogenesis, especially during trabeculation. Crossveinless-2 (CV2, also known as BMP endothelial cell precursor derived regulator [BMPER]) is a BMP-binding protein that modulates the activity of several BMPs. The objective of this study was to examine the combined effects of BMP10 and CV2 on cardiomyocyte differentiation using mouse dedifferentiated fat (mDFAT) cells, which spontaneously differentiate into cardiomyocyte-like cells, as a model. Our results revealed that CV2 binds directly to BMP10, as determined by co-immunoprecipitation, and inhibits BMP10 from initiating SMAD signaling, as determined by luciferase reporter gene assays. BMP10 treatment induced mDFAT cell proliferation, whereas CV2 modulated the BMP10-induced proliferation. Differentiation of cardiomyocyte-like cells proceeded in a reproducible fashion in mDFAT cells, starting with small round Nkx2.5-positive progenitor cells that progressively formed myotubes of increasing length that assembled into beating colonies and stained strongly for Troponin I and sarcomeric alpha-actinin. BMP10 enhanced proliferation of the small progenitor cells, thereby securing sufficient numbers to support formation of myotubes. CV2, on the other hand, enhanced formation and maturation of large myotubes and myotube-colonies and was expressed by endothelial-like cells in the mDFAT cultures. Thus BMP10 and CV2 have important roles in coordinating cardiomyogenesis in progenitor cells.

Original languageEnglish
Pages (from-to)1812-1822
Number of pages11
JournalJournal of Cellular Physiology
Volume233
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

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Bone Morphogenetic Proteins
Skeletal Muscle Fibers
Stem cells
Adipocytes
Cardiac Myocytes
Stem Cells
Fats
Endothelial Cells
Actinin
Troponin I
Endothelial cells
Cell proliferation
Luciferases
Reporter Genes
Immunoprecipitation
Protein Binding
Assays
Carrier Proteins
Genes
Cells

Keywords

  • Actinin
  • Adipocytes
  • Animals
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Homeobox Protein Nkx-2.5
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac
  • Signal Transduction
  • Smad Proteins
  • Stem Cells
  • Troponin I
  • Journal Article

Cite this

Jumabay, M., Zhumabai, J., Mansurov, N., Niklason, K. C., Guihard, P. J., Cubberly, M. R., ... Boström, K. I. (2018). Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells. Journal of Cellular Physiology, 233(3), 1812-1822. https://doi.org/10.1002/jcp.25983

Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells. / Jumabay, Medet; Zhumabai, Jiayinaguli; Mansurov, Nurlan; Niklason, Katharine C; Guihard, Pierre J; Cubberly, Mark R; Fogelman, Alan M; Iruela-Arispe, Luisa; Yao, Yucheng; Saparov, Arman; Boström, Kristina I.

In: Journal of Cellular Physiology, Vol. 233, No. 3, 03.2018, p. 1812-1822.

Research output: Contribution to journalArticle

Jumabay, M, Zhumabai, J, Mansurov, N, Niklason, KC, Guihard, PJ, Cubberly, MR, Fogelman, AM, Iruela-Arispe, L, Yao, Y, Saparov, A & Boström, KI 2018, 'Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells', Journal of Cellular Physiology, vol. 233, no. 3, pp. 1812-1822. https://doi.org/10.1002/jcp.25983
Jumabay, Medet ; Zhumabai, Jiayinaguli ; Mansurov, Nurlan ; Niklason, Katharine C ; Guihard, Pierre J ; Cubberly, Mark R ; Fogelman, Alan M ; Iruela-Arispe, Luisa ; Yao, Yucheng ; Saparov, Arman ; Boström, Kristina I. / Combined effects of bone morphogenetic protein 10 and crossveinless-2 on cardiomyocyte differentiation in mouse adipocyte-derived stem cells. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 3. pp. 1812-1822.
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AU - Zhumabai, Jiayinaguli

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AU - Niklason, Katharine C

AU - Guihard, Pierre J

AU - Cubberly, Mark R

AU - Fogelman, Alan M

AU - Iruela-Arispe, Luisa

AU - Yao, Yucheng

AU - Saparov, Arman

AU - Boström, Kristina I

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AB - Bone morphogenetic protein (BMP) 10, a cardiac-restricted BMP family member, is essential in cardiomyogenesis, especially during trabeculation. Crossveinless-2 (CV2, also known as BMP endothelial cell precursor derived regulator [BMPER]) is a BMP-binding protein that modulates the activity of several BMPs. The objective of this study was to examine the combined effects of BMP10 and CV2 on cardiomyocyte differentiation using mouse dedifferentiated fat (mDFAT) cells, which spontaneously differentiate into cardiomyocyte-like cells, as a model. Our results revealed that CV2 binds directly to BMP10, as determined by co-immunoprecipitation, and inhibits BMP10 from initiating SMAD signaling, as determined by luciferase reporter gene assays. BMP10 treatment induced mDFAT cell proliferation, whereas CV2 modulated the BMP10-induced proliferation. Differentiation of cardiomyocyte-like cells proceeded in a reproducible fashion in mDFAT cells, starting with small round Nkx2.5-positive progenitor cells that progressively formed myotubes of increasing length that assembled into beating colonies and stained strongly for Troponin I and sarcomeric alpha-actinin. BMP10 enhanced proliferation of the small progenitor cells, thereby securing sufficient numbers to support formation of myotubes. CV2, on the other hand, enhanced formation and maturation of large myotubes and myotube-colonies and was expressed by endothelial-like cells in the mDFAT cultures. Thus BMP10 and CV2 have important roles in coordinating cardiomyogenesis in progenitor cells.

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