title: Linkage between the mechanisms of thrombocytopenia and thrombopoiesis.
abstract: Thrombocytopenia is defined as a status in which platelet numbers are reduced. Imbalance between the homeostatic regulation of platelet generation and destruction is 1 potential cause of thrombocytopenia. In adults, platelet generation is a 2-stage process entailing the differentiation of hematopoietic stem cells into mature megakaryocytes (MKs; known as megakaryopoiesis) and release of platelets from MKs (known as thrombopoiesis or platelet biogenesis). Until recently, information about the genetic defects responsible for congenital thrombocytopenia was only available for a few forms of the disease. However, investigations over the past 15 years have identified mutations in genes encoding >20 different proteins that are responsible for these disorders, which has advanced our understanding of megakaryopoiesis and thrombopoiesis. The underlying pathogenic mechanisms can be categorized as (1) defects in MK lineage commitment and differentiation, (2) defects in MK maturation, and (3) defect in platelet release. Using these developmental stage categories, we here update recently described mechanisms underlying megakaryopoiesis and thrombopoiesis and discuss the association between platelet generation systems and thrombocytopenia.
authors.affiliation: Department of Clinical Application Research, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; and.
authors.forename: Koji
authors.identifier: http://orcid.org/0000-0002-5863-7122
authors.initials: K
authors.lastname: Eto
authors.affiliation: Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Shinji
authors.identifier: http://orcid.org/0000-0001-9212-0082
authors.initials: S
authors.lastname: Kunishima
mesh_terms: D000328:Adult; D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D013921:Thrombocytopenia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034061:Thrombopoiesis / Q000235:genetics*