Stem Cell Niche Biology

人体内的特殊细胞，具有生长成许多不同类型细胞的潜力，被称为干细胞。了解干细胞生长成健康或患病成熟细胞的过程有助于揭示人类疾病的发生机制。迄今为止的研究也表明了干细胞如何受到周围环境的影响。例如，在血液中，血液干细胞维持在由骨髓中的专门的“支持细胞”提供的生态系统中。虽然众所周知骨髓微环境有助于骨功能障碍和血癌如白血病，但骨髓“支持细胞”的具体特征和动力学尚不清楚。Tikhonova博士是第一个确定白血病干细胞如何与骨髓相互作用以促进白血病发展的人。这项工作还确定了如何关闭这些元素，从而防止癌症的发展。虽然这项工作突出了微环境在癌症发展中的独特作用，但它也揭示了需要更好地了解化疗等治疗如何操纵微环境来杀死或鼓励癌症发展。Tikhonova博士的加拿大研究主席（CRC）计划旨在通过更好地了解维持造血干细胞的生态系统来解决这些限制。使用最先进的技术，她与临床结果相关的功能基因组研究将揭示骨髓干细胞与其环境之间的对话或“串扰”在正常与疾病状态下的变化。她将扩展这些实验，以检查i）支持急性淋巴细胞白血病（一种骨髓癌症）发展的特定微环境;和ii）免疫系统在微环境中发挥的独特作用，以及它如何促进T细胞急性淋巴细胞白血病的发展，这是一种特别具有侵略性的血癌形式，最常在儿童中诊断。这项工作将提供对造血干细胞与其微环境之间相互作用的全面理解，这将提供关键的见解，有助于设计有效的骨髓功能障碍和血癌治疗方法。

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.