Nature volume 601,pages600–605(2022).

　　人胚狀體模擬早期人類胚胎發(fā)育以及人類胚胎植入子宮過(guò)程

　　Harunobu Kagawa et al.奧地利科學(xué)院分子生物技術(shù)研究所

　　在受精后的一周內(nèi)，人類胚胎會(huì)形成囊胚，并植入子宮。建立人類囊胚模型對(duì)人類生育具有重要意義。但是建立一個(gè)能準(zhǔn)確模擬并符合囊胚不同細(xì)胞類型發(fā)育發(fā)展順序，以及能再現(xiàn)囊胚形態(tài)的模型還存在很大的難度。

　　該研究團(tuán)隊(duì)通過(guò)抑制Hippo、TGF-β和ERK三個(gè)信號(hào)通路，成功利用人多能干細(xì)胞構(gòu)建了人囊胚狀結(jié)構(gòu)（胚狀體）。

　　該研究團(tuán)隊(duì)通過(guò)在人類多能干細(xì)胞中三重抑制Hippo、TGF-β和ERK三個(gè)信號(hào)通路形成胚泡，成功誘導(dǎo)產(chǎn)生了包含三個(gè)原始細(xì)胞譜系（滋養(yǎng)外胚層，外胚層和原始內(nèi)胚層）的囊胚期類似物。另外，該團(tuán)隊(duì)觀察到外胚層誘導(dǎo)極性滋養(yǎng)外胚層的局部成熟，從而賦予囊胚定向附著在激素刺激的子宮內(nèi)膜細(xì)胞上的能力（植入）。

　　a,A schematic of the time window of human peri-implantation development modelled by blastoids(days 5–7).M/MC,morula/morula compacted;B,blastocyst.b,One-step protocol of human blastocyst-like structure formation.N2B27,serum-free medium;PALLY,PD0325901+A83-01+LPA+hLIF+Y-27632.c,Phase-contrast image of human blastocyst-like structures formed on a non-adherent hydrogel microwell array after 96 h.Each microwell is 200μm in diameter.Scale bars,400μm.d,Phase-contrast images of representative human blastocyst-like structures harvested from microwells.Scale bars,200μm(top)and 100μm(bottom).e,Percentages of microwells including a human blastocyst-like structure for different naive PSC lines cultured in the PALLY condition with optimized LPA concentration compared with a H9 control(Ctrl)deprived of the three inhibitors.The morphometric definition of blastocyst-like structures is provided in Methods.n=3 microwell arrays;mean±s.d.f,g,Immunofluorescence of the epiblast(EPI)markers NANOG(yellow)(f)and OCT4(yellow)(g),the TE markers CDX2(cyan)(f)and GATA3(cyan)(g),and the PrE markers SOX17(magenta)(f)and GATA4(magenta)(g)in human blastocyst-like structures.Scale bars,100μm.h,Absolute number of cells positive for OCT4,GATA3 and GATA4(left)and ratios of cells belonging to individual lineages represented as percentage of total number of cells(right)in blastocyst-like structures(96 h)based on immunofluorescence.i,Representative immunofluorescence of the tight junction molecule ZO-1(yellow),the adherence junction molecule CDH1(magenta)and the apical domain molecule aPKC(cyan)in a representative human blastocyst-like structure.Scale bar,50μm.

　　人早期胚胎模型可以較為準(zhǔn)確地模擬早期人類胚胎發(fā)育以及人類胚胎植入子宮過(guò)程。

　　人類早期胚胎模型的建立，為將來(lái)研究人類生育，以及研究人類胚胎早期發(fā)育提供了重要研究基礎(chǔ)。

　　喬森，助理研究員，以第一作者或通訊作者在Endocrinology，ACS Biomater Sci Eng，F(xiàn)ront Neurosci，F(xiàn)ront Molecular Biosciences發(fā)表多篇文章。