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缺氧诱导因子-2α 对躯体神经嵴细胞迁移、增殖和自我更新的重要性。

Hypoxia inducible factor-2α importance for migration, proliferation, and self-renewal of trunk neural crest cells.

机构信息

Translational Cancer Research, Lund University Cancer Center at Medicon Village, Lund University, Lund, Sweden.

Division of Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.

出版信息

Dev Dyn. 2021 Feb;250(2):191-236. doi: 10.1002/dvdy.253. Epub 2020 Sep 26.

DOI:10.1002/dvdy.253
PMID:32940375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7891386/
Abstract

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

神经嵴是一种短暂存在的胚胎干细胞群体。缺氧诱导因子（HIF）-2α与肿瘤中神经嵴干细胞的出现和侵袭性有关。然而，其在正常神经嵴发育中的作用知之甚少。

结果

本文作者表明，HIF-2α在人、鼠和禽类胚胎的躯干部神经嵴细胞中表达。体内敲低或过表达 HIF-2α会导致发育迟缓，诱导神经嵴细胞增殖和自我更新能力，同时减少向交感肾上腺部位迁移的神经嵴细胞比例。反映体内表型，HIF-2α缺失后的转录组变化显示与癌症、侵袭、上皮间质转化和生长阻滞相关的基因富集。

结论

综上所述，这些结果表明，HIF-2α 的表达水平在正常躯干部神经嵴发育过程中必须受到严格控制，而失调的水平会影响与干性、迁移和发育相关的几个重要特征。

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