Stem Cell Niche Biology

点击翻译按钮获取中文摘要

Special human cells within the body that hold the potential to grow into many different types of cells are known as stem cells. Understanding the processes that stem cells use to grow into healthy or diseased mature cells can help uncover how human diseases occur. Research to date has also shown how stem cells can be influenced by their surroundings. For example, within the blood, blood stem cells are maintained within an ecosystem provided by specialized "support cells" in the bone marrow. Although it is well known that the bone marrow microenvironment contributes to bone dysfunction and blood cancers like leukemia, the specific features, and the dynamics of the bone marrow "support cells" are not well understood. Dr. Tikhonova was the first to identify how leukemic stem cells interact with the bone marrow in a way that encourages the development of leukemia. This work also identified how to shut off these elements, which prevents cancer development. While this work highlights the unique role the microenvironment plays in cancer development, it also lays bare the need to better understand how treatments, such as chemotherapy, can manipulate the microenvironment to kill or encourage cancer development. Dr. Tikhonova's Canada Research Chair (CRC) program aims to address these limitations by better understanding the ecosystem in which blood stem cells are maintained. Using state-of-the-art techniques, her functional genomic studies correlated with clinical outcomes will reveal how conversations or `crosstalk' between bone marrow stem cells and their environment changes during normal versus diseased states. She will extend these experiments to examine i) the specific microenvironment that supports the development of acute lymphoblastic leukemia, a cancer of the bone marrow; and ii) the unique role the immune system plays on the microenvironment and how this promotes the development of T-cell acute lymphoblastic leukemia, a particularly aggressive form of blood cancer most commonly diagnosed in children. This work will provide a global understanding of the context in which the interaction between blood stem cells and their microenvironment goes awry, which will provide critical insights that will help design effective treatments for bone marrow dysfunction and blood cancers.