LAUSR

Fetal and neonatal megakaryocyte progenitors are hyperproliferative compared to adult progenitors, and generate large numbers of small, low ploidy megakaryocytes. Historically, these developmental differences were interpreted as "immaturity". However, more recent studies demonstrated that the small and low ploidy fetal/neonatal megakaryocytes have all the characteristics of adult polyploid megakaryocytes, including the presence of granules, a well-developed demarcation membrane system, and proplatelet formation. Thus, rather than immaturity, the features of fetal/neonatal megakaryopoiesis reflect a developmentally unique uncoupling of proliferation, polyploidization and cytoplasmic maturation, which allows fetuses and neonates to populate their rapidly expanding bone marrow and blood volume. At the molecular level, the features of fetal/neonatal megakaryopoiesis result from a complex interplay of developmentally regulated pathways and environmental signals from the different hematopoietic niches. Over the last few years, studies have challenged traditional paradigms about the origin of the megakaryocyte lineage in both fetal and adult life, and the application of single-cell RNA sequencing has led to a better characterization of embryonic, fetal and adult megakaryocytes. In particular, a growing body of data suggest that -at all stages of development- the various functions of megakaryocytes are not fulfilled by the entire megakaryocyte population as a whole, but rather by distinct megakaryocyte sub-populations with dedicated roles. Finally, recent studies have provided novel insights into the mechanisms underlying developmental disorders of megakaryopoiesis, which either uniquely affect fetuses and neonates or have different clinical presentations in neonatal compared to adult life.