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突破性进展!不知国内哪些机构在做这种领先国际前沿的工作?0 D4 q x/ i2 J j
- R/ n" ^3 x( j) J下不了全文,先贴个概要,哪位能找到全文麻烦共享一下,谢谢!
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$ Z2 d1 w$ ~) A" FHighlights
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hESCs are differentiated into TEPs in vitro
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& V: k, s( d' e; E/ a# v, o' VTEP specification requires regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling& d6 `( I; H6 ~ r
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. C* H: d3 X6 JhESC-derived TEPs mature into functional TECs upon transplantation into athymic mice
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TECs support the generation of new T cells that are functional in vitro and in vivo+ }. c2 V7 m& Z* K& `
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Summary! H! O# Y0 R. E2 w
Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional TECs that support T cell development upon transplantation into thymus-deficient mice. Importantly, the engrafted TEPs produce T cells capable of in vitro proliferation as well as in vivo immune responses. Thus, hESC-derived TEP grafts may have broad applications for enhancing engraftment in cell-based therapies as well as restoring age- and stress-related thymic decline. |
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