Spatial profiling of early primate gastrulation in utero.
Spatial profiling of early primate gastrulation in utero.
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DOI：
10.1038/s41586-022-04953-1
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发表时间：
2022-09
期刊：
影响因子：
64.8
通讯作者：
Boroviak TE
中科院分区：
文献类型：
--
作者：
Bergmann S;Penfold CA;Slatery E;Siriwardena D;Drummer C;Clark S;Strawbridge SE;Kishimoto K;Vickers A;Tewary M;Kohler TN;Hollfelder F;Reik W;Sasaki E;Behr R;Boroviak TE
在早期胚胎中，原肠胚形成控制细胞多样性和轴模式的出现。在哺乳动物中，这种转变是由胚胎和胚外组织界面上的动态信号中心协调的。阐明轴在体内形成的分子框架是我们理解人类发育和推进基于干细胞的再生方法的基础。在这里，我们阐明了早期原肠胚的绒猴胚胎在子宫内的空间转录组学和干细胞为基础的胚胎模型。基于高斯过程回归的3D转录组描绘了前内脏内胚层的出现，其特征是保守的（HHEX，LEFTY 2，LHX 1）和灵长类特异性（POL 4，SDC 4，FZD 5）因子。WNT信号传导在空间上协调胚盘中的原条形成，并被SFRP 1/2抵消以维持前域中的多能性。羊膜特化发生在胚胎盘的边界处，通过ID 1/2/3响应BMP信号传导，为灵长类动物多能干细胞（PSC）的羊膜分化提供了发育原理。空间身份定位表明，致敏的绒猴PSC表现出最高的相似性，前胚胎盘，而幼稚的PSC类似于植入前的外胚层。我们的3D转录组模型揭示了灵长类动物胚胎中谱系特化的分子密码，并为破译人类发育提供了体内参考。
Gastrulation controls the emergence of cellular diversity and axis patterning in the early embryo. In mammals, this transformation is orchestrated by dynamic signalling centres at the interface of embryonic and extraembryonic tissues. Elucidating the molecular framework of axis formation in vivo is fundamental for our understanding of human development and to advance stem-cell-based regenerative approaches. Here, we illuminate early gastrulation of marmoset embryos in utero by spatial transcriptomics and stem cell-based embryo models. Gaussian process regression-based 3D-transcriptomes delineate the emergence of the anterior visceral endoderm, which is hallmarked by conserved (HHEX, LEFTY2, LHX1) and primate-specific (POSTN, SDC4, FZD5) factors. WNT signalling spatially coordinates primitive streak formation in the embryonic disc and is counteracted by SFRP1/2 to sustain pluripotency in the anterior domain. Amnion specification occurs at the boundaries of the embryonic disc through ID1/2/3 in response to BMP-signalling, providing a developmental rationale for amnion differentiation of primate pluripotent stem cells (PSCs). Spatial identity mapping demonstrates that primed marmoset PSCs exhibit highest similarity to the anterior embryonic disc, while naïve PSCs resemble the preimplantation epiblast. Our 3D-transcriptome models reveal the molecular code of lineage specification in the primate embryo and provide an in vivo reference to decipher human development.
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DOI：
10.1242/dev.167833
发表时间：
2018-11-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Boroviak T;Stirparo GG;Dietmann S;Hernando-Herraez I;Mohammed H;Reik W;Smith A;Sasaki E;Nichols J;Bertone P
通讯作者：
Bertone P
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
7.7
作者：
Dong, Chen;Beltcheva, Mariana;Theunissen, Thorold W.
通讯作者：
Theunissen, Thorold W.
DOI：
10.1073/pnas.1323697111
发表时间：
2014-01-28
影响因子：
11.1
作者：
Fernandez, Antonio;Huggins, Ian J.;Willert, Karl
通讯作者：
Willert, Karl
影响因子：
4
作者：
HARLOW, CR;HEARN, JP;HODGES, JK
通讯作者：
HODGES, JK