Regulatory mechanisms of PEAR1 expression in myeloid cell-lineage specification.

Platelet Endothelial Aggregation Receptor 1 (PEAR1) is a membrane protein on blood platelets, first described in 2005. Platelets are small circulating cells playing a crucial role in the arrest of bleeding after vascular trauma. Our laboratory revealed that PEAR1 contributes to platelet function by stabilizing the platelet plug, formed upon platelet adhesion to the injured vessel wall and their aggregation to each other. PEAR1 is present on other cells, including endothelial cells, which line the blood vessel surface, but is also expressed in those cells that are the precursors of platelets and in other cells, present in the bone marrow, including granulocyte precursors. The present work aims at understanding the role of PEAR1 in myeloid lineage maturation, i.e. proliferation and differentiation, under normal and pathological conditions, with special focus on its interplay with the transcription factor GATA1. To do so, the project will apply very new methodologies, based on recent insights in gene regulation. Such insights have taught us that control of gene expression is highly complex, involving the structure (DNA sequence), physical organization (chromatin conformation) and interacting proteins (the so-called transcription factors) of a certain genomic region. Some of those features are fixed, such as the genetic component, while others undergo dynamic changes over time, dependent on environmental factors, i.e. the epigenetic component. This work will determine how the reversible expression of PEAR1 participates in bone marrow myeloid differentiation and will clarify whether defective PEAR1 regulation participates in the development of well-defined types of blood cell cancers.

Keywords:Myeloid precursors, Blood cell cancer, PEAR1, Hematopoiesis, Epigenetic regulation, Lineage specification

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences