Developmental changes in human megakaryopoiesis

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.