TET1 facilitates specification of early human lineages including germ cells.
TET1 facilitates specification of early human lineages including germ cells.
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DOI：
10.1016/j.isci.2023.107191
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发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Clark, Amander T.
中科院分区：
文献类型：
--
作者：
Hsu, Fei-Man;Wu, Qiu Ya;Fabyanic, Emily B.;Wei, Alex;Wu, Hao;Clark, Amander T.
TET 1是一种通过5-甲基胞嘧啶（5 mC）转化为5-羟甲基胞嘧啶（5 hmC）的局部DNA去甲基化调节因子。为了研究从人胚胎干细胞（hESC）诱导的人原始生殖细胞样细胞（hPGCLC）中的DNA去甲基化，我们进行了亚硫酸氢盐辅助的APOBEC偶联表观遗传测序（bACEseq），然后进行整合基因组学分析。我们的数据表明，5 hmC富集在hPGCLC特异性NANOG，SOX 17或TFAP 2C结合位点上的hPGCLC诱导，这是伴随着局部DNA去甲基化。使用CRISPR-Cas9，我们表明，当从在小鼠胚胎成纤维细胞上培养的hESC开始时，删除TET 1的催化结构域会降低hPGCLC的能力，并且在将hESC转化为确定的培养基和重组底物后，可以挽救这种表型。总之，我们的研究表明，5 hmC在促进hPGCLC能力的重要性，以及hESC培养条件在调节这种作用中的作用。TET 1在人PGCLC中富集，并由hESC诱导5-羟甲基胞嘧啶（5 hmC）在hPGCLC的基因组中全面升高hPGCLC特异性转录因子（TF）结合位点富集5 hmC在TF结合位点富集伴随靶向去甲基化表观遗传学;发育生物学;胚胎学
Ten Eleven Translocation 1 (TET1) is a regulator of localized DNA demethylation through the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). To examine DNA demethylation in human primordial germ cell-like cells (hPGCLCs) induced from human embryonic stem cells (hESCs), we performed bisulfite-assisted APOBEC coupled epigenetic sequencing (bACEseq) followed by integrated genomics analysis. Our data indicates that 5hmC enriches at hPGCLC-specific NANOG, SOX17 or TFAP2C binding sites on hPGCLC induction, and this is accompanied by localized DNA demethylation. Using CRISPR-Cas9, we show that deleting the catalytic domain of TET1 reduces hPGCLC competency when starting with hESC cultured on mouse embryonic fibroblasts, and this phenotype can be rescued after transitioning hESCs to defined media and a recombinant substrate. Taken together, our study demonstrates the importance of 5hmC in facilitating hPGCLC competency, and the role of hESC culture conditions in modulating this effect. TET1 is enriched in human PGC-like cells (hPGCLCs) with induction from hESCs 5-hydroxymethyl cytosine (5hmC) is globally elevated in the genome of hPGCLCs hPGCLC-specific transcription factor (TF) binding sites enrich with 5hmC 5hmC enrichment at TF binding sites is accompanied by targeted demethylation Epigenetics; Developmental biology; Embryology
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Surani MA
影响因子：
64.5
作者：
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Clark AT
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影响因子：
64.5
作者：
Guo, Fan;Yan, Liying;Qiao, Jie
通讯作者：
Qiao, Jie
影响因子：
23.9
作者：
Ji X;Dadon DB;Powell BE;Fan ZP;Borges-Rivera D;Shachar S;Weintraub AS;Hnisz D;Pegoraro G;Lee TI;Misteli T;Jaenisch R;Young RA
通讯作者：
Young RA
DOI：
10.1523/jneurosci.1821-20.2020
发表时间：
2021-01-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Greer CB;Wright J;Weiss JD;Lazarenko RM;Moran SP;Zhu J;Chronister KS;Jin AY;Kennedy AJ;Sweatt JD;Kaas GA
通讯作者：
Kaas GA