ENDOTHELIAL CELL ROLE IN YOLK SAC STEM CELL DEVELOPMENT

Project: Research project

Description

Our long term research goals are to understand the mechanisms controlling cellular proliferation and differentiation in embryonic blood forming vessels. During embryogenesis, hematopoietic and endothelial cells require common growth factors for formation and may share a common precursor, the hemangioblast. Murine blood cells reportedly arise directly from yolk sac endothelial cells in vitro, however, no in vivo tests of blood cell derivation from endothelium have been performed. We have identified a visceral yolk sac cell population that possesses HSC activity upon transplantation into conditioned newborn mice and we have determined in preliminary studies that this population is comprised of both hematopoietic and endothelial cells. We will use our unique newborn mouse transplantation model to test the hypothesis that endothelial cells formed within the embryonic yolk sac give rise to HSC in vivo, facilitate HSC engraftment upon transplantation into hematologically compromised hosts, and augment HSC expansion ex vivo. Our specific aims are: 1. To determine the potential of endothelial cells to give rise to HSC in vivo. We will use a retroviral marking strategy and reagents that provide isolation of a homogenous population of endothelial cells to determine the clonal relationship of endothelium and blood cells. 2. To determine the capacity of yolk sac endothelial cells to facilitate HSC engraftment upon transplantation into myeloablated hosts. Donor endothelial cells from hematopoietic deficient mice will be injected in varying concentrations with the HSC and repopulating activity measured. 3. To determine if endothelial cells and/or endothelial mitogens alone or in combination with selected hematopoietic growth factors stimulate visceral yolk sac-derived HSC expansion ex vivo. The results of these experiments will provide novel insight into hematopoietic and endothelial cell development during embryogenesis, clarify the role of endothelial-HSC interactions during HSC transplantation, and provide new approaches to modulate HSC proliferative behavior.
StatusFinished
Effective start/end date7/1/993/31/09

Funding

  • National Institutes of Health: $376,250.00
  • National Institutes of Health: $260,442.00
  • National Institutes of Health: $318,504.00
  • National Institutes of Health: $253,112.00
  • National Institutes of Health: $431,518.00
  • National Institutes of Health: $430,359.00
  • National Institutes of Health: $14,246.00
  • National Institutes of Health: $430,277.00
  • National Institutes of Health: $357,727.00
  • National Institutes of Health: $401,529.00

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Yolk Sac
Stem Cells
Endothelial Cells
Blood Cells
Organogenesis
Erythroid Precursor Cells
Fibronectins
Hematopoiesis
Transplantation
Embryonic Structures
Cell Movement
Erythroblasts
Embryoid Bodies
Confocal Microscopy
Embryonic Stem Cells
Hematopoietic Stem Cells
Endothelium
Embryonic Development
Integrins
Intercellular Signaling Peptides and Proteins

ASJC

  • Medicine(all)