4.6 Article

Developmental changes in human megakaryopoiesis

期刊

JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 11, 期 9, 页码 1730-1741

出版社

WILEY
DOI: 10.1111/jth.12326

关键词

cell differentiation; embryonic and fetal development; embryonic stem cell; human development; megakaryocyte; microarray analysis; microRNAs

资金

  1. Agence Nationale de la recherche [ANR-09-BLAN-0275]
  2. Association pour la recherche sur le cancer [ARC 3193]
  3. Labex GR-Ex
  4. program 'Investissements d'avenir'
  5. ANR
  6. Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0275] Funding Source: Agence Nationale de la Recherche (ANR)

向作者/读者索取更多资源

SummaryBackground 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 (hESCs) Methods We optimized the differentiation of MKs from hESCs, and compared these with MKs obtained from primary human hematopoietic tissues at different stages of development. Results Transcriptome analyses revealed a close relationship between hESC-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 (TFs), including MYC and LIN28b, 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 MKs towards hemostasis during ontogeny, and support the idea that MKs derived from hESCs reflect primitive hematopoiesis.

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