Endothelial regulation in cell fate specification during embryonic development of the lung and the hematopoietic system
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Coulombe, Patrick
issued: 2021-04-01T18:02:07Z
issued: 2021
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Embryonic development is a highly coordinated process during which cells undergo regulated division, differentiation, and migration to ultimately shape specialized tissues that perform particular functions. Throughout this course, cell fate is driven by intrinsic cell decisions in response to microenvironmental cues from their surroundings and understanding what governs these processes is at the core of developmental biology. Aberrant expression of essential developmental genes typically elicits apparent embryonic defects due to disruption of normal developmental processes. Thus, investigation of the resulting phenotype in animal models provides valuable insights into their role and overall biological pathways driving organogenesis. The work presented in this dissertation investigates the role of such developmental genes and uncovers significant signaling interactions involving endothelial cells to promote cell specification and maturation of non-vascular cells. First, this study explores the contribution of Sash1 during organogenesis. Examination of Sash1-knockout mouse embryos revealed cell non-autonomous functions in regulating both prenatal lung development and embryonic hematopoiesis. On one hand, endothelial Sash1 signaling in the lung promoted nitric oxide production which plays a critical role in the maturation of alveolar epithelial cells prior to birth. On the other hand, Sash1 expression in non-endothelial cells contributed to the emergence of hematopoietic stem and progenitor cells during the endothelial-to-hematopoietic transition (EHT) in the early embryo. Our findings suggest that Sash1 in the microenvironment impacts the progression of specified hemogenic endothelial cells into hematopoietic clusters and the work presented in chapter 4 identifies multiple candidate cell types as the origin of Sash1 signaling. In addition, early specification of a hemogenic endothelium distinct from its arterial counterpart is a critical event at the origin of EHT. Th…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/77700
note: ENDOTHELIAL REGULATION IN CELL FATE SPECIFICATION DURING EMBRYONIC DEVELOPMENT OF THE LUNG AND THE HEMATOPOIETIC SYSTEM by PATRICK COULOMBE B.Sc. McGill University, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) March 2021 © Patrick Coulombe, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Endothelial regulation in cell fate specification during embryonic development of the lung and the hematopoietic system submitted by Patrick Coulombe in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Dr. Aly Karsan, Pathology Supervisor Dr. Connie Eaves, Medical Genetics Supervisory Committee Member Dr. Kelly McNagny, Medical Genetics Supervisory Committee Member Dr. Fabio Rossi, Medical Genetics University Examiner Dr. Peter Zandstra, Medical Genetics University Examiner Additional Supervisory Committee Members: Dr. Keith Humphries, Medical Genetics Supervisory Committee Member iii ABSTRACT Embryonic development is a highly coordinated process during which cells undergo regulated division, differentiation, and migration to ultimately shape specialized tissues that perform particular functions. Throughout this course, cell fate is driven by intrinsic cell decisions in response to microenvironmental cues from their surroundings and understanding what governs these processes is at the core of developmental biology. Aberrant expression of essential developmental genes typically elicits apparent embryonic defects due to disruption of normal developmental processes. Thus, investigation of the resulting phenotype in animal models provides valuable insights into their role and overall biological pathways driving…
has type: Thesis/Dissertation
date issued: 2021-05
is shown at: 10.14288/1.0396538
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/77700