ESATM · Embryonic stem cell origin of the adipose tissue macrophages

Today insulin resistance (IR) is reaching pandemic proportions and it is predicted to emerge a leading worldwide morbidity by 2030. Immune cells, including the so-called adipose tissue macrophages (ATMs) have key roles in the development of this disease. Pharmacological intervention to shape ATM differentiation and function may be a straightforward approach to prevent or combat IR. However the stem cell origin of ATMs is still unclear, which blocks the development of such prevention or treatment strategies. Recent reports show that some specific sets of macrophages develop from embryonic hematopoietic stem cells (eHSCs) and not from the bone marrow as it was postulated before. Our preliminary studies raise the possibility that eHSCs are present in the mouse and the human adipose tissue and these stem cells replenish the ATMs in adulthood. The major scientific objectives of this project are to (a) address the critical question whether ATMs are derived from eHSCs, and (b) define whether the eHSC-derived ATMs can cause IR. These are novel and non-conventional ideas on the determination of IR and are challenging the current wisdom on ATM origin. The deliverables of this project may open a new path to alleviate or prevent IR through eHSCs.