The role of transposable elements in hematopoietic stem and proginator cell development.

Abstract

Hematopoietic stem cell (HSC) formation is the major developmental process leading to the establishment of the hematopoietic system. HSCs are the foundation of the hematopoietic system and give rise to almost all differentiated hematopoietic cells. HSCs are of high clinical importance as they are used for patients needing a blood transfusion, like in some cases of leukemia. However, as the mechanisms behind the formation of the HSCs are still unexplored, it is hard to find therapeutics against these diseases. Trompouki's lab recently identified that the formation of HSCs during development is mediated by the interplay between RNA sensors involved in innate immune signaling and transposable elements (TEs). The transcripts of transposable elements trigger innate immune receptors like RIG-I and lead to enhanced formation of HSCs. To investigate the role of specific TEs in hematopoiesis, we aim to clone the CRISPR activating and inactivating constructs under a tissue-specific promoter and inject them in zebrafish to generate stable lines. We plan to explore whether overexpression of specific TEs in HSCs or other cell types affects HSC development. We will use whole-mount in situ hybridization, injections, microscopy, and other techniques to dissect the role of specific TEs in developmental hematopoiesis.