β-catenin links cell seeding density to global gene expression during mouse embryonic stem cell differentiation.
β-catenin links cell seeding density to global gene expression during mouse embryonic stem cell differentiation.
复制标题
DOI：
10.1016/j.isci.2021.103541
复制
发表时间：
2022-01-21
期刊：
影响因子：
5.8
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
LeBlanc L;Kim M;Kambhampati A;Son AJ;Ramirez N;Kim J
虽然已知细胞密度会影响许多生物学过程，包括基因表达和细胞命运规范，但缺乏对细胞密度与全局基因调控之间联系的机制理解。在这里，我们揭示了小鼠胚胎干细胞（mESC）中数千个基因的表达受到细胞接种密度的影响，低细胞密度提高了分化效率。从机制上讲，β-连环蛋白在自我更新和高密度分化期间主要定位于粘附连接。然而，当mESC在低密度下分化时，β-连环蛋白易位到细胞核并与Tcf 7 l1缔合，诱导共占据谱系标记。同时，Esrrb维持多能性相关基因的表达，同时在高密度下抑制谱系标记，并且其与DNA的关联在低密度下降低。我们的研究结果提供了新的见解，以前被忽视的，但普遍存在的密度依赖性基因调控的现象。细胞密度影响胚胎干细胞中数千个基因的表达低接种密度通过β-连环蛋白提高分化效率β-连环蛋白与Tcf 7 l1协同作用以诱导谱系标记Esrrb通过抑制其靶点来对抗β-连环蛋白和Tcf 7 l1的作用细胞生物学;干细胞研究;转录组学
Although cell density is known to affect numerous biological processes including gene expression and cell fate specification, mechanistic understanding of what factors link cell density to global gene regulation is lacking. Here, we reveal that the expression of thousands of genes in mouse embryonic stem cells (mESCs) is affected by cell seeding density and that low cell density enhances the efficiency of differentiation. Mechanistically, β-catenin is localized primarily to adherens junctions during both self-renewal and differentiation at high density. However, when mESCs differentiate at low density, β-catenin translocates to the nucleus and associates with Tcf7l1, inducing co-occupied lineage markers. Meanwhile, Esrrb sustains the expression of pluripotency-associated genes while repressing lineage markers at high density, and its association with DNA decreases at low density. Our results provide new insights into the previously neglected but pervasive phenomenon of density-dependent gene regulation. Cell density influences expression of thousands of genes in embryonic stem cells Low seeding density augments differentiation efficiency via β-catenin β-catenin works in tandem with Tcf7l1 for lineage marker induction Esrrb opposes the action of β-catenin and Tcf7l1 by repressing their targets Cell biology; Stem cells research; Transcriptomics
登录
查看更多内容
影响因子：
64.5
作者：
Kim J;Woo AJ;Chu J;Snow JW;Fujiwara Y;Kim CG;Cantor AB;Orkin SH
通讯作者：
Orkin SH
影响因子：
3.7
作者：
Jeon H;Waku T;Azami T;Khoa le TP;Yanagisawa J;Takahashi S;Ema M
通讯作者：
Ema M
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
4.6
作者：
Cha KJ;Kong SY;Lee JS;Kim HW;Shin JY;La M;Han BW;Kim DS;Kim HJ
通讯作者：
Kim HJ
影响因子：
4.6
作者：
Cao, Zubing;Carey, Timothy S.;Knott, Jason G.
通讯作者：
Knott, Jason G.