BMP4 drives primed to naïve transition through PGC-like state.
BMP4 drives primed to naïve transition through PGC-like state.
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DOI：
10.1038/s41467-022-30325-4
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发表时间：
2022-05-19
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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在小鼠和人类干细胞中已经描述了多种多能状态。在这里，我们将单细胞RNA-seq应用于新建立的BMP 4诱导的小鼠向幼稚转变（BiPNT）系统，并表明重置不是细胞命运的直接逆转，而是通过原始生殖细胞样细胞（PGCLC）状态。我们首先发现，上胚层干细胞分为c-Kit+幼稚细胞和c-Kit−滋养层样细胞，其中幼稚分支通过PGCLC中间体进一步过渡，能够在体内发生精子。从机制上讲，我们表明DOT 1 L抑制部分通过促进Gata 3/6的H3 K79 me 2损失而允许从引发的多能性向PGCLC的转变。此外，Prdm 1/Blimp 1是PGCLC和幼稚细胞所必需的，而Gata 2通过促进滋养层样命运来抑制PGC-like状态。我们的工作不仅揭示了一种从启动到幼稚转变的替代途径，而且还深入了解了生殖细胞的发育。在小鼠和人类干细胞中已经描述了多种多能状态。在本文中，作者描述了BMP 4诱导的引发向幼稚转变期间的轨迹，该转变分叉为幼稚和滋养层样分支，幼稚分支处具有PGC样中间体。
Multiple pluripotent states have been described in mouse and human stem cells. Here, we apply single-cell RNA-seq to a newly established BMP4 induced mouse primed to naïve transition (BiPNT) system and show that the reset is not a direct reversal of cell fate but goes through a primordial germ cell-like cells (PGCLCs) state. We first show that epiblast stem cells bifurcate into c-Kit+ naïve and c-Kit− trophoblast-like cells, among which, the naïve branch undergoes further transition through a PGCLCs intermediate capable of spermatogenesis in vivo. Mechanistically, we show that DOT1L inhibition permits the transition from primed pluripotency to PGCLCs in part by facilitating the loss of H3K79me2 from Gata3/6. In addition, Prdm1/Blimp1 is required for PGCLCs and naïve cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to naïve transition, but also gains insight into germ cell development. Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naïve transition, which bifurcates into naïve and trophoblast-like branches with a PGC-like intermediate at the naïve branch.
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DOI：
10.1073/pnas.1708341114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Krendl C;Shaposhnikov D;Rishko V;Ori C;Ziegenhain C;Sass S;Simon L;Müller NS;Straub T;Brooks KE;Chavez SL;Enard W;Theis FJ;Drukker M
通讯作者：
Drukker M
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
16
作者：
Cecere, Germano;Hoersch, Sebastian;Jensen, Morten B.;Dixit, Shiv;Grishok, Alla
通讯作者：
Grishok, Alla
影响因子：
5.9
作者：
Hackett JA;Kobayashi T;Dietmann S;Surani MA
通讯作者：
Surani MA
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic