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Biomechanical forces promote embryonic haematopoiesis

机译：生物力学促进胚胎造血作用

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摘要

Biomechanical forces are emerging as critical regulators of embryo-genesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runxl (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells4. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runxl in CD41~+_c-Kit~~+ haematopoietic progenitor cells, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.
机译：生物力学力量正在成为胚胎发生的关键调节器，特别是在正在发展的心血管系统中。在脊椎动物心跳开始后，位于背主动脉腹侧，胎盘血管以及脐动脉和卵黄动脉内衬的细胞会启动转录因子Runxl的表达（参考文献3-5），这是造血功能的主要调节因子，上升到造血细胞4。尚不清楚在这个发育阶段施加在血管壁上的生物力学力是否可作为造血潜能的决定因素。在这里，使用体外分化的小鼠胚胎干细胞，我们显示流体剪切应力增加了CD41〜__c-Kit ~~ +造血祖细胞中Runxl的表达，从而增加了它们的造血集落形成潜能。此外，我们发现剪切应力增加了小鼠胚胎的主动脉副内脏/主动脉性腺-中肾上皮细胞的造血集落形成潜能和造血标志物的表达，并且废除了一氧化氮（剪应力诱导的信号传导的介质）在体外和体内损害了造血潜能。这些数据共同揭示了生物力学在造血发育中的关键作用。

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  • 来源
    《Nature》 |2009年第25期|1131-11351162|共6页
  • 作者

    Luigi Adamo; Olaia Naveiras; Pamela L. Wenzel; Shannon McKinney-Freeman; Peter J. Mack; Jorge Gracia-Sancho; Astrid Suchy-Dicey; Momoko Yoshimoto; M. William Lensch; Mervin C. Yoder; Guillermo Garcia-Cardena; George Q. Daley;

  • 作者单位

    Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.;

    Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Division of Hematology, Brigham and Women's Hospital Harvard Stem Cell Institute Manton Center for Orphan Disease Research Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.;

    Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Division of Hematology, Brigham and Women's Hospital Harvard Stem Cell Institute Manton Center for Orphan Disease Research Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.;

    Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Division of Hematology, Brigham and Women's Hospital Harvard Stem Cell Institute Manton Center for Orphan Disease Research Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.;

    Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.;

    Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.;

    Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.;

    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.;

    Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Division of Hematology, Brigham and Women's Hospital Harvard Stem Cell Institute Manton Center for Orphan Disease Research Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.;

    Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.;

    Center for Excellence in Vascular Biology, Departments of Pathology Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.;

    Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Division of Hematology, Brigham and Women's Hospital Harvard Stem Cell Institute Manton Center for Orphan Disease Research Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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