Matched Developmental Timing of Donor Cells with the Host Is Crucial for Chimera Formation.

Matched Developmental Timing of Donor Cells with the Host Is Crucial for Chimera Formation.
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供体细胞与宿主的匹配的发育时机对于嵌合体的形成至关重要。

DOI:
10.1016/j.stemcr.2018.03.004
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发表时间:
2018-05-08
期刊:
影响因子:
5.9
通讯作者:
Jaenisch R
Jaenisch R
中科院分区:
医学1区
文献类型:
--
作者:
Cohen MA;Markoulaki S;Jaenisch R

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通过将多能干细胞注射到桑椹胚至胚泡阶段的小鼠胚胎中或通过将更成熟的细胞引入到与供体细胞的分化阶段相对应的后期胚胎中来产生嵌合小鼠。然而,尚未严格测试成功的嵌合体形成是否需要宿主胚胎和供体细胞的发育阶段相匹配。在这里,我们比较了嵌合体的成功形成后注射的初级神经嵴细胞(NCC)到囊胚或胚胎干细胞(ESCs)到E8.5胚胎(异时注射)与注射ESCs细胞到囊胚或NCC到E8.5胚胎(等时注射)。嵌合体的形成是有效的供体和宿主相匹配时,但没有功能嵌合体的贡献,发现在异时注射。这表明,供体细胞的发育阶段与宿主胚胎相匹配对于供体细胞功能性植入发育中的胚胎至关重要。供体细胞和宿主的发育匹配对于嵌合体的形成至关重要。将ESC异时注射到E8.5小鼠胚胎中未能产生嵌合体。将NCC注射到胚泡中未能形成嵌合体,即使细胞凋亡受损。Cohen等人比较了ESC和NCC异时和等时注射中嵌合体形成的效率。使用两种不同的和良好表征的植入前和植入后嵌合平台,他们表明供体细胞和宿主的发育年龄匹配对于嵌合体形成至关重要。
Chimeric mice have been generated by injecting pluripotent stem cells into morula-to-blastocyst stage mouse embryo or by introducing more mature cells into later stage embryos that correspond to the differentiation stage of the donor cells. It has not been rigorously tested, however, whether successful chimera formation requires the developmental stage of host embryo and donor cell to be matched. Here, we compared the success of chimera formation following injection of primary neural crest cells (NCCs) into blastocysts or of embryonic stem cells (ESCs) into E8.5 embryos (heterochronic injection) with that of injecting ESCs cells into the blastocyst or NCCs into the E8.5 embryos (isochronic injection). Chimera formation was efficient when donor and host were matched, but no functional chimeric contribution was found in heterochronic injections. This suggests that matching the developmental stage of donor cells with the host embryo is crucial for functional engraftment of donor cells into the developing embryo. Developmental matching of donor cells and host is crucial for chimera formation Heterochronic injection of ESCs to E8.5 mouse embryos failed to yield chimeras NCCs injected to blastocyst failed to form chimeras, even when apoptosis is impaired Cohen at al. compares the efficiency of chimera formation in heterochronic and isochronic injections of ESCs and NCCs. Using two distinct and well-characterized pre- and post-implantation chimeric platforms, they show that matching of developmental age of donor cells and the host is essential for chimera formation.
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