Loss of the Epigenetic Mark 5-hmC in Psoriasis: Implications for Epidermal Stem Cell Dysregulation.
Loss of the Epigenetic Mark 5-hmC in Psoriasis: Implications for Epidermal Stem Cell Dysregulation.
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DOI：
10.1016/j.jid.2019.10.016
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Murphy GF
中科院分区：
文献类型：
--
作者：
Li F;Yuan CW;Xu S;Zu T;Woappi Y;Lee CAA;Abarzua P;Wells M;Ramsey MR;Frank NY;Wu X;Mandinova A;Frank MH;Lian CG;Murphy GF
表观遗传调控对干细胞在正常发育过程中的命运有着深远的影响，以维持生理组织的稳态。在这里，我们报告减少10 - 11易位（泰特）甲基胞嘧啶双加氧酶的表达和DNA羟甲基化标记，5-羟甲基胞嘧啶（5-hmC）的损失，角质形成细胞干细胞（KSC）和过境扩增细胞（TAC）在人类银屑病和咪喹莫特诱导的小鼠银屑病。5-hmC的缺失与KSC动力学失调相关，导致巢蛋白和表达FABP 5的TAC积累，产生经典的银屑病表皮结构。此外，5-hmC的损失伴随着减少TET 1和TET 2 mRNA的表达。小鼠银屑病表皮5-hmC的全基因组定位显示，在调节干细胞稳态的基因中，包括MBD 1、RTN 1、STRN 4、PRKD 2、AKT 1、MAPKAP 2以及与RAR和Wnt/β-catenin信号通路相关的基因中，5-hmC的位点特异性丢失。在体外恢复泰特表达的抗坏血酸在培养的人KSC中完成，以显示类似的[Ca++]诱导的分化，导致5-hmC水平增加和巢蛋白表达减少。据我们所知，银屑病与干细胞失调相关的表观遗传缺陷以前尚未报道。这一观察结果提出了一种可能性，即影响泰特-5-hmC通路的表观遗传修饰剂可能是迄今为止未被认识到的治疗效用的相关方法。
Epigenetic regulation has profound influence on stem cell fate during normal development in maintenance of physiologic tissue homeostasis. Here we report diminished ten-eleven translocation (TET) methylcytosine dioxygenase expression and loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), in keratinocyte stem cells (KSCs) and transit-amplifying cells (TACs) in human psoriasis and in imiquimod-induced murine psoriasis. Loss of 5-hmC was associated with dysregulated KSC kinetics, resulting in accumulation of nestin and FABP5-expressing TACs to produce classic psoriatic epidermal architecture. Moreover, 5-hmC loss was accompanied by diminished TET1 and TET2 mRNA expression. Genome-wide mapping of epidermal 5-hmC in murine psoriasis revealed loci-specific loss of 5-hmC in genes regulating stem cell homeostasis, including MBD1, RTN1, STRN4, PRKD2, AKT1, MAPKAP2, as well as those associated with RAR and Wnt/β-catenin signaling pathways. In vitro restoration of TET expression by ascorbic acid was accomplished in cultured human KSCs to show similar [Ca++]-induced differentiation, resulting in increased 5-hmC levels and reduced nestin expression. To our knowledge, an epigenetic deficiency in psoriasis with relevance to stem cell dysregulation has not been previously reported. This observation raises the possibility that epigenetic modifiers that impact on the TET-5-hmC pathway may be a relevant approach of heretofore unappreciated therapeutic utility.
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DOI：
10.1111/bjd.15610
发表时间：
2017-07
期刊：
The British journal of dermatology
影响因子：
--
作者：
Griffiths CEM;van der Walt JM;Ashcroft DM;Flohr C;Naldi L;Nijsten T;Augustin M
通讯作者：
Augustin M
MiR-125b 通过靶向巢蛋白来协调神经干/祖细胞的细胞增殖、分化和迁移
影响因子：
2.4
作者：
Cui Y;Xiao Z;Han J;Sun J;Ding W;Zhao Y;Chen B;Li X;Dai J
通讯作者：
Dai J
影响因子：
64.5
作者：
Hsu YC;Li L;Fuchs E
通讯作者：
Fuchs E
通过维生素C治疗对黑色素瘤细胞的表观遗传重编程。
影响因子：
5.7
作者：
Gustafson CB;Yang C;Dickson KM;Shao H;Van Booven D;Harbour JW;Liu ZJ;Wang G
通讯作者：
Wang G
影响因子：
64.5
作者：
Cimmino L;Dolgalev I;Wang Y;Yoshimi A;Martin GH;Wang J;Ng V;Xia B;Witkowski MT;Mitchell-Flack M;Grillo I;Bakogianni S;Ndiaye-Lobry D;Martín MT;Guillamot M;Banh RS;Xu M;Figueroa ME;Dickins RA;Abdel-Wahab O;Park CY;Tsirigos A;Neel BG;Aifantis I
通讯作者：
Aifantis I