Mouse prenatal platelet-forming lineages share a core transcriptional program but divergent dependence on MPL
Details
Publication Year 2015-08-06, Volume 126, Issue #6, Page 807-16
Journal Title
Blood
Publication Type
Journal Article
Abstract
The thrombopoietic environment of the neonate is established during prenatal life, therefore a comprehensive understanding of platelet-forming cell development during embryogenesis is critical to understanding the etiology of early onset thrombocytopenia. The recent discovery that the first platelet forming cells of the conceptus are not megakaryocytes (MKs) but diploid platelet-forming cells (DPFCs) revealed a previously unappreciated complexity in thrombopoiesis. This raises important questions, including: When do conventional MKs appear?; Do pathogenic genetic lesions of adult MKs affect DPFCs?; What role does MPL, a key regulator of adult megakaryopoiesis, play in prenatal platelet-forming lineages? We have performed a comprehensive study to determine the spatial and temporal appearance of prenatal platelet-forming lineages. We demonstrate that DPFCs originate in the yolk sac and then rapidly migrate to other extra- and intra-embryonic tissues. Using gene disruption models of Gata1 and Nfe2, we demonstrate that perturbing essential adult MK genes causes an analogous phenotype in the early embryo prior to the onset of hematopoietic stem/progenitor cell-driven (definitive) hematopoiesis. Finally, we present the surprising finding that DPFC and MK commitment from their respective precursors is MPL-independent in vivo, but that completion of MK differentiation and establishment of the prenatal platelet mass is dependent on MPL expression.
Publisher
ASH
WEHI Research Division(s)
Cancer And Haematology; Molecular Medicine
PubMed ID
25995324
NHMRC Grants
NHMRC/1016647
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2015-06-15 09:53:28
Last Modified: 2015-11-19 11:58:27
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