OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification.
OCT4-mediated inflammation induces cell reprogramming at the origin of cardiac valve development and calcification.
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DOI：
10.1126/sciadv.abf7910
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发表时间：
2021-11-05
期刊：
影响因子：
13.6
通讯作者：
Puceat M
中科院分区：
文献类型：
--
作者：
Farrar EJ;Hiriart E;Mahmut A;Jagla B;Peal DS;Milan DJ;Butcher JT;Puceat M
细胞重编程是瓣膜钙化的起源。细胞可塑性通过维持祖细胞的分化潜能在胚胎中起着关键作用。出生后的体细胞是否会恢复到胚胎样的幼稚状态，重新获得可塑性，并重新分化为导致疾病的细胞类型，这仍然是一个有趣的问题。利用遗传谱系追踪和单细胞RNA测序，我们揭示了Oct 4在胚胎第9.5天由核因子κB（NFκB）诱导，在心内膜向间充质转化开始时，来自前心脏形成区的小鼠内皮细胞亚群中。这些细胞获得了软骨成骨的命运。成年主动脉瓣细胞中的OCT 4导致小鼠和人瓣膜的钙化。这些钙化细胞起源于Oct 4胚胎谱系。内皮细胞系中Pou 5 f1（Pit-Oct-Unc，OCT 4）的基因缺失可防止ApoE−/−小鼠瓣膜的主动脉狭窄和钙化。我们建立了以前未鉴定的自身细胞重编程NFκB和OCT 4介导的炎症通路，触发了瓣膜钙化的剂量依赖性机制。
Cell reprogramming is at the origin of valve calcification. Cell plasticity plays a key role in embryos by maintaining the differentiation potential of progenitors. Whether postnatal somatic cells revert to an embryonic-like naïve state regaining plasticity and redifferentiate into a cell type leading to a disease remains intriguing. Using genetic lineage tracing and single-cell RNA sequencing, we reveal that Oct4 is induced by nuclear factor κB (NFκB) at embyronic day 9.5 in a subset of mouse endocardial cells originating from the anterior heart forming field at the onset of endocardial-to-mesenchymal transition. These cells acquired a chondro-osteogenic fate. OCT4 in adult valvular aortic cells leads to calcification of mouse and human valves. These calcifying cells originate from the Oct4 embryonic lineage. Genetic deletion of Pou5f1 (Pit-Oct-Unc, OCT4) in the endocardial cell lineage prevents aortic stenosis and calcification of ApoE−/− mouse valve. We established previously unidentified self-cell reprogramming NFκB- and OCT4-mediated inflammatory pathway triggering a dose-dependent mechanism of valve calcification.
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影响因子：
1.6
作者：
Chakraborty, Santanu;Combs, Michelle D.;Yutzey, Katherine E.
通讯作者：
Yutzey, Katherine E.
DOI：
10.3390/e22030296
发表时间：
2020-03-04
期刊：
Entropy (Basel, Switzerland)
影响因子：
--
作者：
Albergante L;Mirkes E;Bac J;Chen H;Martin A;Faure L;Barillot E;Pinello L;Gorban A;Zinovyev A
通讯作者：
Zinovyev A
影响因子：
14
作者：
Farrar, Emily J.;Pramil, Varsha;Richards, Jennifer M.;Mosher, Christopher Z.;Butcher, Jonathan T.
通讯作者：
Butcher, Jonathan T.
雏鸡和小鼠心内膜垫的空间转录曲线在体外鉴定了内膜EMT的新调节剂。
影响因子：
5
作者：
DeLaughter DM;Christodoulou DC;Robinson JY;Seidman CE;Baldwin HS;Seidman JG;Barnett JV
通讯作者：
Barnett JV
影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA