Long non coding RNA Role in iPSC derived Megakaryocyte Development and Leukemia

Abstract

Megakaryocytes (MKs) are rare polyploid cells found in the bone marrow specially newlineknown as mother cell for platelets. Platelets are small colorless enucleated cell fragments that newlineare critical to vascular hemostasis and wound healing as well as in inflammation. Several newlineblood disorders characterized by dysfunctional platelets result in prolonged bleeding time, newlinedefective clot formation and bleeding tendency. Thrombocytopenia is one of the most newlinecommon hematologic disorders, characterized by an abnormally low number of platelets and newlineit affects both children and adults. Thrombocytopenia is sometimes a first sign of newlinehematologic malignancies, infectious diseases, thrombotic micro angiopathies and newlineautoimmune disorders, and is also a common side effect of many medications. There is no newlinespecific therapy for the vast majority and only severe cases need to be treated. Currently, in newlinevitro generation of MKs from human induced pluripotent stem cell (hiPSC)-derived platelets newlinetechnology is a good treatment option, could provide an alternative source of platelets for newlinetreating thrombocytopenic patients in different disease conditions. Recent advancement in the newlinerapidly evolving field of hematological epigenetics have shown the role of non-coding RNAs newline(ncRNAs) such as microRNAs (miRNAs) and long ncRNAs (lncRNAs) in the context of newlineblood cell development. However, there are only few studies which have identified and newlinecharacterized the lncRNA expression profiles in MKs, the underlying regulatory mechanisms newlinegoverned by lncRNAs has not been explored for the normal development of MKs lineage as newlinewell as in disease condition. We hypothesized that lncRNAs are differentially expressed in newlineMKs, therefore might play a critical role in the normal development and regulation of newlinemegakaryocytopoiesis. Our studies aimed to establish a protocol for the generation of MKs in newlinexeno-free and defined conditions, and to determine the lncRNA profile and molecular newlinemechanism in hiPSC-derived MKs, as well as in hyper-proliferative clinical condition i.e. newlineAcute Megakar