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Developmental changes in human megakaryopoiesis
Author(s) -
Bluteau O.,
Langlois T.,
RiveraMunoz P.,
Favale F.,
Rameau P.,
Meurice G.,
Dessen P.,
Solary E.,
Raslova H.,
Mercher T.,
Debili N.,
Vainchenker W.
Publication year - 2013
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12326
Subject(s) - biology , megakaryocyte , haematopoiesis , ontogeny , microbiology and biotechnology , transcriptome , embryonic stem cell , transcription factor , function (biology) , embryogenesis , cellular differentiation , stem cell , gene , gene expression , genetics , embryo
Summary Background The molecular bases of the cellular changes that occur during human megakaryocyte ( MK ) ontogeny remain unknown, and may be important for understanding the significance of MK differentiation from human embryonic stem cells (h ESC s) Methods We optimized the differentiation of MK s from h ESC s, and compared these with MK s obtained from primary human hematopoietic tissues at different stages of development. Results Transcriptome analyses revealed a close relationship between h ESC ‐derived and fetal liver‐derived MKs, and between neonate‐derived and adult‐derived MKs. Major changes in the expression profiles of cell cycle and transcription factors ( TF s), including MYC and LIN 28b, and MK‐specific regulators indicated that MK maturation progresses during ontogeny towards an increase in MK ploidy and a platelet‐forming function. Important genes, including CXCR4 , were regulated by an on–off mechanism during development. Discussion Our analysis of the pattern of TF network and signaling pathways was consistent with a growing specialization of MK s towards hemostasis during ontogeny, and support the idea that MK s derived from h ESC s reflect primitive hematopoiesis.