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Delineating the Cardio-Myogenic Hierarchy during Mouse Embryonic Development.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Delineating the Cardio-Myogenic Hierarchy during Mouse Embryonic Development./
Author:	Yoon, Charles.
Description:	1 online resource (147 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 79-12(E), Section: B.
Contained By:	Dissertation Abstracts International79-12B(E).
Subject:	Biomedical engineering. -
Online resource:	click for full text (PQDT)
ISBN:	9780438189850

Delineating the Cardio-Myogenic Hierarchy during Mouse Embryonic Development.
Yoon, Charles.

Delineating the Cardio-Myogenic Hierarchy during Mouse Embryonic Development. - 1 online resource (147 pages)

Source: Dissertation Abstracts International, Volume: 79-12(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2018.

Includes bibliographical references

The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. We have turned to cell surface mass spectrometry to increase the candidate pool of membrane proteins on cardiac progenitor cells (CPCs). Specifically, we examined the expression of surface markers on CPCs using an integrated mass spectrometry and microarray-based approach. We analyzed the genome and surface proteome of cardiac progenitors generated from the stage-specific differentiation of mouse (m) and human (h) pluripotent stem cells (PSCs). We have identified and characterized Frizzled 4 (FZD4) as a new marker for lateral plate mesoderm (LPM). We also utilized FZD4 as a marker, in conjunction with fetal liver kinase 1 (FLK1) and platelet derived growth factor alpha (PDGFRA) and demonstrated an increase in CPC purity and a subsequent increase in cardiomyocyte (CM) enrichment. Additionally, we have found FZD4 is also expressed in the hPSC system and results in a similar enrichment in CM. Furthermore, we showed that NORRIN can be presented to the FZD4 receptor to induce Wingless-related integration site (WNT) signaling-mediated proliferation, resulting in an increase in CM output from CPCs. This demonstrates the value in knowing the set of surface markers present on a cell at a specific stage of development and the potential to leverage that knowledge into more efficient cell differentiation protocols. Further validation of the function of FZD4 is also being established in a preliminary in vivo study. The identified surface markers also have the potential to isolate cell types not only within the CPC stage, but within the PSC, epiblast, and primitive streak stages as well. These markers have been compiled into a preliminary cell-cell communication network model overlaid with an initial alternative slicing analysis to determine potential mechanisms that impact cell signaling during early CPC development. In summary, the application of a systems biology approach as demonstrated in this thesis, greatly expanded the number of surface markers available and upon further characterization and validation, can improve our understanding of cardiac biology.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780438189850Subjects--Topical Terms:

588770
Biomedical engineering.
Index Terms--Genre/Form:

554714
Electronic books.

Delineating the Cardio-Myogenic Hierarchy during Mouse Embryonic Development.
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520 $a The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. We have turned to cell surface mass spectrometry to increase the candidate pool of membrane proteins on cardiac progenitor cells (CPCs). Specifically, we examined the expression of surface markers on CPCs using an integrated mass spectrometry and microarray-based approach. We analyzed the genome and surface proteome of cardiac progenitors generated from the stage-specific differentiation of mouse (m) and human (h) pluripotent stem cells (PSCs). We have identified and characterized Frizzled 4 (FZD4) as a new marker for lateral plate mesoderm (LPM). We also utilized FZD4 as a marker, in conjunction with fetal liver kinase 1 (FLK1) and platelet derived growth factor alpha (PDGFRA) and demonstrated an increase in CPC purity and a subsequent increase in cardiomyocyte (CM) enrichment. Additionally, we have found FZD4 is also expressed in the hPSC system and results in a similar enrichment in CM. Furthermore, we showed that NORRIN can be presented to the FZD4 receptor to induce Wingless-related integration site (WNT) signaling-mediated proliferation, resulting in an increase in CM output from CPCs. This demonstrates the value in knowing the set of surface markers present on a cell at a specific stage of development and the potential to leverage that knowledge into more efficient cell differentiation protocols. Further validation of the function of FZD4 is also being established in a preliminary in vivo study. The identified surface markers also have the potential to isolate cell types not only within the CPC stage, but within the PSC, epiblast, and primitive streak stages as well. These markers have been compiled into a preliminary cell-cell communication network model overlaid with an initial alternative slicing analysis to determine potential mechanisms that impact cell signaling during early CPC development. In summary, the application of a systems biology approach as demonstrated in this thesis, greatly expanded the number of surface markers available and upon further characterization and validation, can improve our understanding of cardiac biology.
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