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 (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.
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 (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.
Authors: Megan S Rost; Ilya Shestopalov; Yang Liu; Andy H Vo; Catherine E Richter; Sylvia M Emly; Francesca G Barrett; David L Stachura; Michael Holinstat; Leonard I Zon; Jordan A Shavit Journal: Blood Adv Date: 2018-12-11
Authors: Massiel Chavez Stolla; Seana C Catherman; Paul D Kingsley; R Grant Rowe; Anne D Koniski; Katherine Fegan; Leah Vit; Kathleen E McGrath; George Q Daley; James Palis Journal: Blood Adv Date: 2019-01-08
Authors: Kamaleldin E Elagib; Chih-Huan Lu; Goar Mosoyan; Shadi Khalil; Ewelina Zasadzińska; Daniel R Foltz; Peter Balogh; Alejandro A Gru; Deborah A Fuchs; Lisa M Rimsza; Els Verhoeyen; Miriam Sansó; Robert P Fisher; Camelia Iancu-Rubin; Adam N Goldfarb Journal: J Clin Invest Date: 2017-05-08 Impact factor: 14.808
Authors: Ji-Yoon Noh; Shilpa Gandre-Babbe; Yuhuan Wang; Vincent Hayes; Yu Yao; Paul Gadue; Spencer K Sullivan; Stella T Chou; Kellie R Machlus; Joseph E Italiano; Michael Kyba; David Finkelstein; Jacob C Ulirsch; Vijay G Sankaran; Deborah L French; Mortimer Poncz; Mitchell J Weiss Journal: J Clin Invest Date: 2015-05-11 Impact factor: 14.808
Authors: Viola Lorenz; Haley Ramsey; Zhi-Jian Liu; Joseph Italiano; Karin Hoffmeister; Sihem Bihorel; Donald Mager; Zhongbo Hu; William B Slayton; Benjamin T Kile; Martha Sola-Visner; Francisca Ferrer-Marin Journal: Thromb Haemost Date: 2017-12-06 Impact factor: 5.249