The product of BMP-directed differentiation protocols for human primed pluripotent stem cells is placental trophoblast and not amnion.

The product of BMP-directed differentiation protocols for human primed pluripotent stem cells is placental trophoblast and not amnion.
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DOI:
10.1016/j.stemcr.2022.04.014
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发表时间:
2022-06-14
期刊:
影响因子:
5.9
通讯作者:
Tuteja, Geetu
Tuteja, Geetu
中科院分区:
医学1区
文献类型:
--
作者:
Seetharam, Arun S.;Vu, Ha T. H.;Choi, Sehee;Khan, Teka;Sheridan, Megan A.;Ezashi, Toshihiko;Roberts, R. Michael;Tuteja, Geetu

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当FGF2和激活素信号被最小化时,通过暴露于骨形态发生蛋白-4(BMP4),多能干细胞(PSCs)可以产生滋养层细胞(TB)的观察最近受到了挑战,表明该过程相反地产生羊膜。在这里,通过分析来自多个来源的转录组数据,包括批量和单细胞数据,我们表明BMP4程序产生的真正的结核与胎盘绒毛结核和结核干细胞产生的结核相似。分析还表明,胚胎羊膜和不同形式的结核病之间的转录签名具有共性。我们的数据为继续使用来源于PSCs的结核病作为研究胎盘发育的模型提供了理由。使用BAP法分化的细胞更像TB而不是胚胎羊膜偏离标准BAP法导致分化较低的TB单细胞/核RNA-seq分析鉴定出两个合体滋养层细胞群Tuteja、Roberts及其同事证明,通过使用标准化(BAP)方案中的BMP4诱导的人类多能干细胞分化出的细胞更类似于滋养层细胞,并且存在于妊娠早期胎盘中,而不是胚胎羊膜。他们还表明,所使用的特定BAP方案影响了结核病的分化率。
The observation that trophoblast (TB) can be generated from primed pluripotent stem cells (PSCs) by exposure to bone morphogenetic protein-4 (BMP4) when FGF2 and ACTIVIN signaling is minimized has recently been challenged with the suggestion that the procedure instead produces amnion. Here, by analyzing transcriptome data from multiple sources, including bulk and single-cell data, we show that the BMP4 procedure generates bona fide TB with similarities to both placental villous TB and TB generated from TB stem cells. The analyses also suggest that the transcriptomic signatures between embryonic amnion and different forms of TB have commonalities. Our data provide justification for the continued use of TB derived from PSCs as a model for investigating placental development. Cells differentiated by using BAP protocols resemble TB more than embryonic amnion Deviation from the standard BAP protocol results in less differentiated TB Single-cell/nucleus RNA-seq analysis identifies two syncytiotrophoblast populations Tuteja, Roberts, and colleagues show that cells differentiated from primed human pluripotent stem cells by using BMP4 in a standardized (BAP) protocol more closely resemble trophoblast differentiated from trophoblast stem cells and present in first-trimester placenta than embryonic amnion. They also demonstrate that the specific BAP protocol used impacts the rate of differentiation toward TB.
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