干细胞及其治疗学.pptVIP

ESC in developmental biology to study the role of specific genes in development; to isolate early-stage populations; to identify progenitors that represent novel stages of hematopoietic, vascular, and neural development; to define the factors that regulate primary germ layer induction. Human stem cells as a model for cardiac differentiation and disease Hematopoietic stem cell development is dependent on blood flow. Cell. 2009 May 15;137(4):736-48. During vertebrate embryogenesis, hematopoietic stem cells (HSCs) arise in the aorta-gonads-mesonephros (AGM) region. We report here that blood flow is a conserved regulator of HSC formation. In zebrafish, chemical blood flow modulators regulated HSC development, and silent heart (sih) embryos, lacking a heartbeat and blood circulation, exhibited severely reduced HSCs. Flow-modifying compounds primarily affected HSC induction after the onset of heartbeat; however, nitric oxide (NO) donors regulated HSC number even when treatment occurred before the initiation of circulation, and rescued HSCs in sih mutants. Morpholino knockdown of nos1 (nnos/enos) blocked HSC development, and its requirement was shown to be cell autonomous. In the mouse, Nos3 (eNos) was expressed in HSCs in the AGM. Intrauterine Nos inhibition or embryonic Nos3 deficiency resulted in a reduction of hematopoietic clusters and transplantable murine HSCs. This work links blood flow to AGM hematopoiesis and identifies NO as a conserved downstream regulator of HSC development. Biomechanical forces promote embryonic haematopoiesis Nature. 2009 May 13. [Epub ahead of print] Links . Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. 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