Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naïve pluripotency under inhibition of protein kinase C.
Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naïve pluripotency under inhibition of protein kinase C.
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蛋白激酶 C 抑制下核小体重塑和脱乙酰化复合物以及 MBD3 影响小鼠胚胎干细胞幼稚多能性
DOI：
10.1038/s41420-022-01131-0
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发表时间：
2022-08-01
影响因子：
7
通讯作者：
Du, Fuliang
中科院分区：
文献类型：
--
作者：
Dai, Yujian;Sun, Jialei;He, Na;An, Liyou;Hou, Chunhui;Du, Fuliang
幼稚小鼠胚胎干细胞（mES）的多能性受到多种信号通路的调节，其中蛋白激酶C（PKCi）的抑制在维持幼稚mES中发挥特别重要的作用。然而，核小体重塑和脱乙酰酶（NuRD）复合物在PKCi系统中培养的mES中的调节功能尚不清楚。我们发现，与2 iL衍生的mES相比，PKC i衍生的mES显示出NuRD复合物亚基的低mRNA表达，包括MBD 3、HDAC 1/HDAC 2、MTA 1和RbAP 46/RbAP 48。Western印迹显示，PKCi衍生的mES在第3代表达较低水平的MBD 3和HDAC 2，以及在第10代表达较低水平的MBD 3、HDAC 2和MTA 1，表明PKCi抑制NuRD复合物的表达。MBD 3的敲低通过增加NANOG和OCT 4表达和集落形成来增加PKC i衍生的mES多能性。相比之下，MBD 3的过表达或去除PKC介导的mES分化，导致NANOG、OCT 4和REX 1表达和集落形成减少，分化相关基因表达增加，并分化为扁平细胞。mES中的MBD 3在PKC抑制剂去除后的敲低部分逆转了细胞分化。我们的研究结果表明，调节NuRD复合物及其MBD 3亚基影响在PKCi系统中培养的mES的幼稚多能性。
The pluripotency of naïve mouse embryonic stem cells (mES) is regulated by multiple signaling pathways, with inhibition of protein kinase C (PKCi) playing a particularly important role in maintaining naïve mES. However, the regulatory function of nucleosome remodeling and deacetylase (NuRD) complex in mES cultured in a PKCi system is unknown. We found that, compared with 2iL-derived mES, PKCi-derived mES showed low mRNA expression of NuRD complex subunits, including MBD3, HDAC1/HDAC2, MTA1, and RbAP46/RbAP48. Western blot showed that PKCi-derived mES expressed lower protein levels of MBD3 and HDAC2 at passage 3, as well as MBD3, HDAC2, and MTA1 at passage 10, indicating that PKCi suppressed NuRD complex expression. Knockdown of MBD3 increased PKCi-derived mES pluripotency by increasing NANOG and OCT4 expression and colony formation. By contrast, overexpression of MBD3 or removal of PKC inhibitor-induced differentiation of mES, results in reduced NANOG, OCT4, and REX1 expression and colony formation, increased differentiation-related gene expression, and differentiation into flat cells. Knockdown of MBD3 in mES upon PKC inhibitor removal partially reversed cell differentiation. Our results show that the regulatory NuRD complex and its MBD3 subunit influence the naïve pluripotency of mES cultured in a PKCi system.
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影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
64.5
作者：
Soldner F;Hockemeyer D;Beard C;Gao Q;Bell GW;Cook EG;Hargus G;Blak A;Cooper O;Mitalipova M;Isacson O;Jaenisch R
通讯作者：
Jaenisch R
影响因子：
16
作者：
Xue, YT;Wong, JM;Wang, WD
通讯作者：
Wang, WD
影响因子：
5.2
作者：
Hayashi, Yohei;Furue, Miho Kusuda;Asashima, Makoto
通讯作者：
Asashima, Makoto
影响因子：
23.9
作者：
Hu, Guang;Wade, Paul A.
通讯作者：
Wade, Paul A.