SATB1 promotion of trophoblast stem cell renewal through regulation of threonine dehydrogenase.
SATB1 promotion of trophoblast stem cell renewal through regulation of threonine dehydrogenase.
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DOI：
10.1016/j.bbagen.2020.129757
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Soares MJ
中科院分区：
文献类型：
--
作者：
Kubota K;Iqbal K;Soares MJ
滋养细胞干细胞（Trophoblast stem， TS）的更新和分化是胎盘形成的重要过程。特殊AT-rich binding protein 1 （SATB1）是TS细胞干细胞状态的关键调控因子。在本研究中，我们确定了SATB1下游靶点并研究了它们的作用。在表达对照或Satb1短发夹rna （shRNAs）的Rcho-1 TS细胞中进行rna测序分析，以确定Satb1候选靶点。差异调控转录物通过逆转录-定量聚合酶链反应验证。利用功能缺失法研究了SATB1的靶标l -苏氨酸3-脱氢酶（TDH）在滋养细胞发育调控中的作用。在SATB1敲低TS细胞的差异调控转录本中，已知影响TS细胞干细胞状态的下调转录本和滋养层细胞分化特征的上调转录本。Tdh的表达对SATB1的失调反应灵敏。Tdh在TS细胞干细胞状态下表达较高，随着TS细胞分化而表达降低。用TDH抑制剂或TDH特异性shRNA处理Rcho-1 TS细胞可抑制细胞增殖，降低TS细胞干细胞状态相关转录本的表达，提高滋养细胞分化相关转录本的表达。TDH破坏可降低TS细胞集落大小、Cdx2表达和囊胚生长。我们的研究结果表明，SATB1对TS细胞维持的作用至少部分是通过TDH的调节和作用介导的。控制TS细胞动力学的调控途径决定了胎盘的功能、妊娠结局和产后健康。
Trophoblast stem (TS) cell renewal and differentiation are essential processes in placentation. Special AT-rich binding protein 1 (SATB1) is a key regulator of the TS cell stem state. In this study, we identified SATB1 downstream targets and investigated their actions. RNA-sequencing analysis was performed in Rcho-1 TS cells expressing control or Satb1 short hairpin RNAs (shRNAs) to identify candidate SATB1 targets. Differentially regulated transcripts were validated by reverse transcription-quantitative polymerase chain reaction. The role of a target of SATB1, L-threonine 3-dehydrogenase (TDH), in the regulation of trophoblast cell development was investigated using a loss-of-function approach. Among the differentially regulated transcripts in SATB1 knockdown TS cells, were downregulated transcripts known to affect the TS cell stem state and upregulated transcripts characteristic of trophoblast cell differentiation. Tdh expression was exquisitely responsive to SATB1 dysregulation. Tdh expression was high in the TS cell stem state and decreased as TS cells differentiated. Treatment of Rcho-1 TS cells with a TDH inhibitor or a TDH specific shRNA inhibited cell proliferation and attenuated the expression of TS cell stem state-associated transcripts and elevated the expression of trophoblast cell differentiation-associated transcripts. TDH disruption decreased TS cell colony size, Cdx2 expression, and blastocyst outgrowth. Our findings indicate that the actions of SATB1 on TS cell maintenance are mediated, at least in part, through the regulation and actions of TDH. Regulatory pathways controlling TS cell dynamics dictate the functionality of the placenta, pregnancy outcomes, and postnatal health.
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DOI：
10.1242/dev.144139
发表时间：
2017-04-15
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Goolam M;Zernicka-Goetz M
通讯作者：
Zernicka-Goetz M
DOI：
10.1126/science.1226603
发表时间：
2013-01-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shyh-Chang N;Locasale JW;Lyssiotis CA;Zheng Y;Teo RY;Ratanasirintrawoot S;Zhang J;Onder T;Unternaehrer JJ;Zhu H;Asara JM;Daley GQ;Cantley LC
通讯作者：
Cantley LC
影响因子：
2.5
作者：
Pan, Zishu;Sikandar, Shaheen;Lipkin, Steven M.
通讯作者：
Lipkin, Steven M.
影响因子：
1.5
作者：
Lee, Dong-Soo;Rumi, M. A. Karim;Konno, Toshihiro;Soares, Michael J.
通讯作者：
Soares, Michael J.
DOI：
10.1073/pnas.1111312108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Alexander, Peter B.;Wang, Jian;McKnight, Steven L.
通讯作者：
McKnight, Steven L.