title: Genomic landscape of megakaryopoiesis and platelet function defects.
abstract: Megakaryopoiesis is a complex, stepwise process that takes place largely in the bone marrow. At the apex of the hierarchy, hematopoietic stem cells undergo a number of lineage commitment decisions that ultimately lead to the production of polyploid megakaryocytes. On average, megakaryocytes release 10(11) platelets per day into the blood that repair vascular injuries and prevent excessive bleeding. This differentiation process is tightly controlled by exogenous and endogenous factors, which have been the topics of intense research in the hematopoietic field. Indeed, a skewing of megakaryocyte commitment and differentiation may entail the onset of myeloproliferative neoplasms and other preleukemic disorders together with acute megakaryoblastic leukemia, whereas quantitative or qualitative defects in platelet production can lead to inherited platelet disorders. The recent advent of next-generation sequencing has prompted mapping of the genomic landscape of these conditions to provide an accurate view of the underlying lesions. The aims of this review are to introduce the physiological pathways of megakaryopoiesis and to present landmark studies on acquired and inherited disorders that target them. These studies have not only introduced a new era in the fields of molecular medicine and targeted therapies but may also provide us with a better understanding of the mechanisms underlying normal megakaryopoiesis and thrombopoiesis that can inform efforts to create alternative sources of megakaryocytes and platelets.
authors.affiliation: Centre for Regenerative Medicine Stefano Ferrari, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; and.
authors.forename: Elisa
authors.identifier: http://orcid.org/0000-0002-6110-5944
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Centre for Regenerative Medicine Stefano Ferrari, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; and Haematopoietic Stem Cell Biology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Norfo
authors.affiliation: Centre for Regenerative Medicine Stefano Ferrari, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; and.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pennucci
authors.affiliation: Centre for Regenerative Medicine Stefano Ferrari, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; and.
authors.forename: Roberta
authors.identifier: http://orcid.org/0000-0001-6657-0864
authors.initials: R
authors.lastname: Zini
authors.affiliation: Centre for Regenerative Medicine Stefano Ferrari, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; and.
authors.forename: Rossella
authors.identifier: http://orcid.org/0000-0003-0660-6110
authors.initials: R
authors.lastname: Manfredini
mesh_terms: D000818:Animals; D001791:Blood Platelet Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D034061:Thrombopoiesis / Q000235:genetics*