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Ho, Kevin

University of British Columbia

Hematopoiesis is a process where blood cells with distinct functions are produced from hematopoietic stem cells. This process is regulated, both biochemically and biophysically, by a specialized microenvironment called the hematopoietic niche. The niche facilitates blood cell development and maintains blood cell homeostasis. To achieve hematopoietic homeostasis, two critical components are required: 1) a coordinated cell fate decision among hematopoietic stem and progenitor cells and 2) a functional hematopoietic niche that shapes an appropriate signaling environment for the resident stem cells. To gain a fundamental understanding of how the two components are regulated, I use Drosophila hematopoiesis as a genetically tractable model system for studying hematopoiesis. Specifically, I study the behavior of hematopoietic progenitor cells in their endogenous environment (Chapter 2). Next, I build upon these findings to investigate the direct cell-cell communication between hematopoietic progenitor cells (Chapter 3), and the development, regulation, and maintenance of the hematopoietic niche (Chapter 4). In Chapter 2, I develop a long-term whole organ culture system for the Drosophila hematopoietic organ, the lymph gland. Using this approach, I track the location and real-time kinetics of blood cell differentiation and proliferation, both in homeostatic and pathogenic conditions. In Chapter 3, I describe the molecular and cellular mechanism that coordinates the behaviors of hematopoietic progenitors. Specifically, I identify that the hematopoietic progenitors are incorporated in a signaling network that functions to equilibrate information across a large population of progenitors to guide their collective cell fate decision. In Chapter 4, I describe the molecular and cellular mechanism that facilitates the coordination of the activity of hematopoietic niche cells. My findings suggest that the hematopoietic niche is organized in a signaling network established by gap junctions. The network maintains proper niche architecture, allows bi-directional communication between niche cells, and creates a healthy niche microenvironment for developing hematopoietic progenitors. Together, my research provides mechanistic and fundamental insights into how hematopoietic activities are regulated to meet developmental and immunological needs.

Text

2023-12-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/86770

Cell and Developmental Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/