Speaker: Raquel Espin Palazon, assistant professor in Iowa State University Department of Genetics, Development and Cell Biology
Title: “Inflammation as a natural phenomenon that orchestrates Hematopoietic Stem Cell formation”
Abstract: Hematopoietic stem cells (HSCs) are rare cells within human bone marrow that are responsible both for the life-long replenishment of all blood cell lineages and for the curative effects of bone marrow transplantation. The creation of human induced pluripotent stem cells holds great promise for cellular regeneration therapies, but it is not currently possible to instruct these cells to generate bona fide HSCs in vitro. There is therefore an urgent need to understand the signals that instruct HSC fate in vivo in order to replicate HSC generation in vitro for clinical utility. In the Espin lab, we work on the identification and characterization of novel molecular cues that trigger HSC formation. Since our discovery that inflammatory signals are required for HSC formation (Espin-Palazon, Cell 2014), we are committed to decipher how these signals that have been studied in the context of injury and infection but not normal development, instruct HSC fate. We combine the power of in vivo imaging that the zebrafish model possesses and its genetic amenability to generate unique genetic tools that are allowing us to decipher from an unprecedented view how NFkB acts as the switch that turns on Notch signaling for HSC formation. We have also discovered that the pattern recognition receptor Nod1 activates RipK2, both essential for HSC fate. These experiments would not be possible in a mammalian system, where in vivo visualization takes place by intravital imaging, causing inflammation that will alter any readout derived from it. These, in combination with recent developed chromatin profiling techniques and low input RNA libraries are allowing us to understand the enigmatic role that inflammatory signals play during HSC development.