Lineage Establishment and Progression within the Inner Cell Mass of the Mouse Blastocyst Requires FGFR1 and FGFR2.
Lineage Establishment and Progression within the Inner Cell Mass of the Mouse Blastocyst Requires FGFR1 and FGFR2.
复制标题
DOI：
10.1016/j.devcel.2017.05.003
复制
发表时间：
2017-06-05
影响因子：
11.8
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Kang M;Garg V;Hadjantonakis AK
FGF4是小鼠胚泡内细胞团（ICM）内原始内胚层（PrE）与多能外胚层（EPI）的关键信号驱动特化。为了深入了解ICM细胞内对FGF4应答的受体，我们将单细胞分辨率定量成像与野生型和Fgf受体（Fgfr）突变胚胎的单细胞转录组学相结合。尽管FGFR2具有PrE特异性表达，但所有ICM细胞均表达FGFR1，这对于确定PrE身份至关重要。还需要通过FGFR1的信号传导来限制EPI细胞中多能性相关因子NANOG的水平。然而，这两种受体的活性是ICM内谱系建立所必需的。534个单个ICM细胞的基因表达谱确定了与每个受体相关的不同下游靶点。这些数据使我们提出了一个模型，其中ICM内的FGFR1和FGFR2的独特和附加活性协调建立两个不同的谱系。FGF4是小鼠胚泡内细胞团中驱动谱系特化的关键信号。Kang等人使用单细胞转录组学的单细胞分辨率定量成像来阐明FGF受体FGFR 1和FGFR 2的相对需求，以抑制FGF 4信号，并确定FGFR 1在原始内胚层特化中至关重要。
FGF4 is the key signal driving specification of primitive endoderm (PrE) versus pluripotent epiblast (EPI) within the inner cell mass (ICM) of the mouse blastocyst. To gain insight into the receptor(s) responding to FGF4 within ICM cells, we combined single-cell-resolution quantitative imaging with single-cell transcriptomics of wild-type and Fgf receptor (Fgfr) mutant embryos. Despite the PrE-specific expression of FGFR2, it is FGFR1, expressed by all ICM cells, which is critical for establishment of a PrE identity. Signaling through FGFR1 is also required to constrain levels of the pluripotency-associated factor NANOG in EPI cells. However, the activity of both receptors is required for lineage establishment within the ICM. Gene expression profiling of 534 single ICM cells identified distinct downstream targets associated with each receptor. These data lead us to propose a model whereby unique and additive activities of FGFR1 and FGFR2 within the ICM coordinate establishment of two distinct lineages. FGF4 is the key signal driving lineage specification within the mouse blastocyst inner cell mass. Kang et al. use single-cell-resolution quantitative imaging with single-cell transcriptomics to elucidate relative requirements of FGF receptors FGFR1 and FGFR2 to transduce the FGF4 signal and establish FGFR1 as critical in primitive endoderm specification.
登录
查看更多内容
影响因子：
10.5
作者：
Brewer JR;Mazot P;Soriano P
通讯作者：
Soriano P
影响因子：
10.5
作者：
Brewer JR;Molotkov A;Mazot P;Hoch RV;Soriano P
通讯作者：
Soriano P
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
4.6
作者：
Artus, Jerome;Panthier, Jean-Jacques;Hadjantonakis, Anna-Katerina
通讯作者：
Hadjantonakis, Anna-Katerina
影响因子：
2.7
作者：
Krawchuk, Dayana;Honma-Yamanaka, Nobuko;Yamanaka, Yojiro
通讯作者：
Yamanaka, Yojiro