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Foxc1 Regulates Early Cardiomyogenes...

Lambers, Erin.

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Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells./
Author:	Lambers, Erin.
Description:	270 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.
Contained By:	Dissertation Abstracts International77-10B(E).
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10117202
ISBN:	9781339786056

Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells.
Lambers, Erin.

Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells. - 270 p.

Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2016.

Embryonic Stem Cells (ESCs) hold great potential for regeneration of damaged myocardium, however the molecular circuitry that guides ESC differentiation into cardiomyocytes remains poorly understood. This is exemplified by the elusive role of the transcription factor, Foxc1, during cardiac development. The only known Foxc1 target during heart development is Tbx1. Because Foxc1 null mice contain heart mutations that are far more severe than Tbx1 null mice, it is likely that Foxc1 has additional regulatory roles during heart development. The goal of our study was to test whether Foxc1 is critical for ESC differentiation into functional cardiomyocytes through proper regulation of specific downstream gene networks. Converging evidence from Foxc1 deficient and overexpression ESC models reveals a close relationship between Foxc1 levels and early cardiomyogenic factors Isl1, Mef2c, and Nkx2.5 and also the production of functional cardiomyocytes. We show Foxc1 regulates early cardiomyogenesis during a specific window of differentiation, D4-D6. Through whole transcriptome RNA-sequencing analysis, we report pathways regulated by Foxc1 involved in cardiac function including actin cytoskeleton, cell adhesion, tight and gap junctions, and calcium signaling. Our data indicate a novel Foxc1 direct gene target, Myh7, which encodes the predominant myosin heavy chain isoform, MHCbeta, expressed during cardiac development. These data lead us to conclude that Foxc1 regulates both early cardiomyogenesis and the functional properties of ESC-derived cardiomyocytes. Our findings shed light on the molecular circuitry governing cardiomyogenesis that may lead to the development of better translational strategies for the use of pluripotent stem cells in regenerative medicine towards repairing damaged myocardium.

ISBN: 9781339786056Subjects--Topical Terms:

3172791
Cellular biology.

Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells.
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100 1 $a Lambers, Erin. $3 3192764
245 1 0 $a Foxc1 Regulates Early Cardiomyogenesis and Cardiomyocyte Function from Embryonic Stem Cell Derived Stem Cells.
300 $a 270 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.
500 $a Advisers: Tsutomu Kume; Gangjian Qin.
502 $a Thesis (Ph.D.)--Northwestern University, 2016.
520 $a Embryonic Stem Cells (ESCs) hold great potential for regeneration of damaged myocardium, however the molecular circuitry that guides ESC differentiation into cardiomyocytes remains poorly understood. This is exemplified by the elusive role of the transcription factor, Foxc1, during cardiac development. The only known Foxc1 target during heart development is Tbx1. Because Foxc1 null mice contain heart mutations that are far more severe than Tbx1 null mice, it is likely that Foxc1 has additional regulatory roles during heart development. The goal of our study was to test whether Foxc1 is critical for ESC differentiation into functional cardiomyocytes through proper regulation of specific downstream gene networks. Converging evidence from Foxc1 deficient and overexpression ESC models reveals a close relationship between Foxc1 levels and early cardiomyogenic factors Isl1, Mef2c, and Nkx2.5 and also the production of functional cardiomyocytes. We show Foxc1 regulates early cardiomyogenesis during a specific window of differentiation, D4-D6. Through whole transcriptome RNA-sequencing analysis, we report pathways regulated by Foxc1 involved in cardiac function including actin cytoskeleton, cell adhesion, tight and gap junctions, and calcium signaling. Our data indicate a novel Foxc1 direct gene target, Myh7, which encodes the predominant myosin heavy chain isoform, MHCbeta, expressed during cardiac development. These data lead us to conclude that Foxc1 regulates both early cardiomyogenesis and the functional properties of ESC-derived cardiomyocytes. Our findings shed light on the molecular circuitry governing cardiomyogenesis that may lead to the development of better translational strategies for the use of pluripotent stem cells in regenerative medicine towards repairing damaged myocardium.
590 $a School code: 0163.
650 4 $a Cellular biology. $3 3172791
650 4 $a Molecular biology. $3 517296
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773 0 $t Dissertation Abstracts International $g 77-10B(E).
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