Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.
Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.
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DOI：
10.1038/s41556-022-01075-8
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发表时间：
2023-03
影响因子：
21.3
通讯作者：
Brickman, Joshua M.
中科院分区：
文献类型：
--
作者：
Wong, Yan Fung;Kumar, Yatendra;Proks, Martin;Herrera, Jose Alejandro Romero;Rothova, Michaela Mrugala;Monteiro, Rita S.;Pozzi, Sara;Jennings, Rachel E.;Hanley, Neil A.;Bickmore, Wendy A.;Brickman, Joshua M.
细胞增殖对于几乎所有需要增加细胞数的发育和分化阶段都是基本的。尽管细胞周期阶段与分化有关，但实际的增殖过程尚未被视为具有特定作用。在这里，我们利用了人类胚胎干细胞衍生的内胚层祖细胞，我们发现这是腹膜前腹的体外模型。这些细胞在分化效率上表现出扩展的胰腺祖细胞的分化效率的提高，这些祖先与染色质可及性水平和谱系实用增强子的退役水平上的器官特异性增强子启动有关。我们的发现表明，胚胎发育中的细胞增殖大约不仅仅是组织膨胀。需要确保基因调节网络的平衡，使细胞能够启动以进行未来的分化。因此，谱系特异性中间体的扩展可能是实现体外分化高保真性的重要步骤。
Wong等。报道说，扩大人类胚胎干细胞衍生的内皮胚胎祖细胞是腹侧的模型，通过该模型，他们通过该模型确定了祖细胞扩张与增强子景观中组织特异性变化之间的联系。
Cell proliferation is fundamental for almost all stages of development and differentiation that require an increase in cell number. Although cell cycle phase has been associated with differentiation, the actual process of proliferation has not been considered as having a specific role. Here we exploit human embryonic stem cell-derived endodermal progenitors that we find are an in vitro model for the ventral foregut. These cells exhibit expansion-dependent increases in differentiation efficiency to pancreatic progenitors that are linked to organ-specific enhancer priming at the level of chromatin accessibility and the decommissioning of lineage-inappropriate enhancers. Our findings suggest that cell proliferation in embryonic development is about more than tissue expansion; it is required to ensure equilibration of gene regulatory networks allowing cells to become primed for future differentiation. Expansion of lineage-specific intermediates may therefore be an important step in achieving high-fidelity in vitro differentiation. Wong et al. report that expanding human embryonic stem cell-derived endodermal progenitors serve as a ventral foregut model, through which they identify a link between progenitor expansion and tissue-specific changes in the enhancer landscape.
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影响因子：
21.3
作者：
通讯作者：
--
一个3D系统，用于建模人类胰腺发育及其参考单细胞转录组图集，并确定祖细胞扩展所需的信号通路。
影响因子：
16.6
作者：
Gonçalves CA;Larsen M;Jung S;Stratmann J;Nakamura A;Leuschner M;Hersemann L;Keshara R;Perlman S;Lundvall L;Thuesen LL;Hare KJ;Amit I;Jørgensen A;Kim YH;Del Sol A;Grapin-Botton A
通讯作者：
Grapin-Botton A
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.2
作者：
Hay, David C.;Zhao, Debiao;Cui, Wei
通讯作者：
Cui, Wei
影响因子：
5.9
作者：
Akbari, Soheil;Sevinc, Gulben Gurhan;Erdal, Esra
通讯作者：
Erdal, Esra