We are currently extending our study on the role of the hematopoietic microenvironment in the regulation of adult HSCs to embryonic and pathological (neoplastic and non-neoplastic) situations. We are establishing their stem cell signature by analyzing their transcriptomic and proteomic profiles and studying the role of mutual instructions in the maintenance/induction of their stem cell properties, including quiescence, chimoresistance, proliferation and differentiation. To reach our objectives, we have developed new technologies to isolate and characterize quiescent chemoresistant human HSCs (SP ALDH cells) as well as to mimic their complex interactions with BM niches (in vitro human 3D niche [patent # WO2013/024096FR] and in vivo xenograft models) (cf Figure 3). Access to patient's biological samples relies on French and International clinical and research networks developed since several years.
Project 1: To optimize our in vitro and in vivo 3D human hematopoietic niche models to encompass human pathological situations,
Project 2: To extend the role of hematopoietic niches in HSC regulation to human embryos,
Project 3: To understand the role of hematopoietic niches in the pathogenesis of neoplasia such as myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML) as well as in the chemoresistance of leukemic stem cells,
Project 4: To study the role of mutual interactions between HSCs, osteocompetent cells and endothelial cells in the processes of bone tissue repair and ectopic development.