Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells.
Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells.
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DOI：
10.1002/dvdy.253
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Mohlin S
中科院分区：
文献类型：
--
作者：
Niklasson CU;Fredlund E;Monni E;Lindvall JM;Kokaia Z;Hammarlund EU;Bronner ME;Mohlin S
神经脊是一个暂时性的胚胎干细胞群体。缺氧诱导因子-2α与肿瘤中神经脊干细胞的出现和侵袭性有关。然而，人们对它在正常神经脊发育中的作用知之甚少。在这里，我们证明了缺氧诱导因子-2α在人、小鼠和禽类胚胎的主干神经脊细胞中表达。体内HIF-2α的敲除和过表达导致神经脊细胞的发育延迟、增殖和自我更新能力，同时降低了神经脊细胞向交感肾上腺部位迁移的比例。HIF-2α缺失后的转录组变化反映了体内的表型，揭示了与癌症、侵袭、上皮向间充质转化和生长停滞相关的基因的丰富。综上所述，这些结果表明，在正常的躯干神经脊发育过程中，必须严格控制HIF-2α的表达水平，并且异常水平影响与茎、迁移和发育有关的几个重要特征。HIF-2α在人、小鼠和禽类胚胎的干神经脊细胞中表达上调或下调HIF-2α影响干神经脊细胞迁移和增殖敲除HIF-2α促进干神经脊细胞自我更新
The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)‐2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. Here, we show that HIF‐2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF‐2α in vivo causes developmental delays, induces proliferation, and self‐renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF‐2α reveal enrichment of genes associated with cancer, invasion, epithelial‐to‐mesenchymal transition, and growth arrest. Taken together, these results suggest that expression levels of HIF‐2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development. HIF‐2α is expressed in trunk neural crest cells in human, mouse and avian embryos Up‐ or downregulation of HIF‐2α affects trunk neural crest cell migration and proliferation Knockout of HIF‐2α enhances trunk neural crest cell self‐renewal RNA sequencing data reflects the in vivo phenotype
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作者：
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通讯作者：
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