A Gap-Junction-Mediated, Calcium-Signalling Network Controls Blood Progenitor Fate Decisions in Hematopoiesis
This week we profile a recent publication in Current Biology from the lab of
Dr. Guy Tanentzapf (pictured, fourth from right) at UBC.
Can you provide a brief overview of your lab’s current research focus?
Stem cells are essential for animal development and allow the maintenance and regeneration of tissues. Stem cells retain the capability to divide and to develop into many types of adult cells throughout the lifetime of an organism. The blood stem cells in humans and animals are particularly important for fighting infections as they produce the immune cells required to fight infection. A major project in our lab seeks to understand the mechanisms that regulate the activation of blood stem cells such that they produce immune cells upon infection. A key feature of blood stem cells is that although there are many hundreds of them dispersed over relatively large distances, their behaviour is remarkably well coordinated. Our work focuses on trying to understand the mechanisms by which the behaviour of blood stem cells is synchronised. In particular, we focus on how blood stem cells exchange signals with one another to form a network. Our general model is that this network allows blood stem cells to act in a coordinated fashion. In response to infection, a subset of blood stem cells change their behaviour and signal to their neighbours to induce them to alter their behaviour as well. Understanding the mechanisms that allow the coordination of blood stem cell function will help us gain insight into what happens in diseases that involve dysregulation of the blood stem cells such as leukemia and autoimmune diseases.
What is the significance of the findings in this publication?
Our new paper uses live imaging of calcium signalling in the intact Drosophila lymph gland, where blood stem cells reside in flies. We show that gap-junctions, a special type of cell junctions that form channels between neighbouring cells, connects blood stem cells in a network. This gap junction-mediated network between blood stem cells ensures uniform encoding and processing of calcium signals. By ensuring such a uniform pattern of calcium signalling in the hundreds of progenitors in the lymph glands, this network allows coordinated cell-fate decisions among the blood stem cells. The implications of our work are substantial. Gap-junctions between blood stem cells are a common conserved feature of hematopoiesis, the process of blood cell differentiation from stem cells. Since changes in gap-junction mediated communication in blood progenitors have been extensively implicated in blood pathologies such as acute myelogenous leukemia (AML), our work may prove relevant to the etiology of diseases that involve a change in blood stem cell homeostasis. For these reasons, we think our paper is an important contribution and a major conceptual advancement with possible wide clinical relevance.
What are the next steps for this research?
A major aim of our future studies is to gain further and more specific understanding of how infection changes the network linking blood stem cells in order to control blood cell production.
If you’d like to mention your funding sources, please list them.
Work in our lab is funded by grants from the Canadian Institute for Health Research and the Natural Science and Engineering Research Council of Canada.