Dynamic Change of the Hematopoietic Stem Cell Niche
Ever since the conceptualization of the hematopoietic stem cell (HSC) niche by Schofield in 1978, much of niche research has focused on the identification of the most potent and influential niche cells within the bone marrow (BM). However, given that different hematopoietic stress factors dramatically impact the HSC niche, much is still to be learned about the heterogeneity, dynamics, function, and interactions of niche cells. To that end, this session will examine novel methods (e.g., in vivo live imaging, and mass spectrometry-based analyses of soluble factors or single cell niche dissection), that allow for the detection of minute changes on reserve and active HSCs and niche cells under short and long-term hematopoietic stress.
Dr. Hitoshi Takizawa will discuss how dormant HSCs are activated to self-renew and differentiate to increase blood production upon enhanced hematopoietic need. It remains unclear how HSCs and progenitor cells (HSPCs) integrate the peripheral demand signal to facilitate hematopoietic production and what the biological consequence of HSPCs activation is on cell fate decision. To that end, he will also discuss the mechanistic insights on how HSPCs sense pathogen insult through innate immune receptors and orchestrate hematopoiesis for host defense and tissue homeostasis.
Dr. Marieke Essers will discuss infections associated with extensive consumption of differentiated hematopoietic cells, representing a high risk for health. The mechanisms coordinating the rapid and efficient regeneration of these differentiated cells during such stress conditions remain unclear. In addition to identifying how HSCs respond under inflammatory conditions, she will also focus on investigating the response of the BM niche to inflammatory stress and how different components of the BM niche support the response of quiescent HSCs to inflammatory stress in vivo.
Dr. Tannishtha Reya will address how high-resolution in vivo imaging can be used to map normal stem cell behavior and interactions within living animals. She will describe how these interactions are driven by adhesive signals, and how they change during cancer formation. She will also highlight mechanisms that drive therapy resistance in the treatment of cancers. Dr. Reya's research focuses on the signals that control stem cell self-renewal and how these signals are hijacked in cancer. Using a series of genetic models, she has studied how classic developmental signaling pathways influence hematopoietic stem cell growth and regeneration as well as leukemia development when such pathways are dysregulated. Through this work she has determined that the cell fate determinant Musashi, plays a critical role in driving progression of hematologic malignancies and solid cancer and can be potential target for diagnostics and therapy.
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