小柯机器人

南澳大利亚大学Natasha L. Harvey研究团队发现，一个Prox1增强子在淋巴管系统中抑制造血。这一研究成果于2023年1月25日在线发表在国际学术期刊《自然》上。

研究人员描述了一种新的增强子元件，它对调节Prox1在淋巴内皮细胞中的表达很重要。这种演化上保守的增强子与关键的淋巴转录调控因子结合，包括GATA2、FOXC2、NFATC1和PROX1。研究人员对增强子进行了基因组编辑来去除围绕Gata2结合位点的5个核苷酸，这导致纯合子突变小鼠因严重的淋巴血管缺陷而围产期死亡。增强子突变小鼠的淋巴内皮细胞表现出淋巴内皮细胞特征基因的表达减少和造血内皮特征基因的表达增加，并获得了生成造血细胞的能力。

这些数据不仅揭示了一种对调节Prox1表达和淋巴内皮细胞身份很重要的转录增强子元件，而且还证明了淋巴内皮具有通常被Prox1抑制的生血能力。

据介绍，转录增强子元件负责协调基因表达的时间和空间控制，这对发育过程中编程细胞身份至关重要。

附：英文原文

Title: A Prox1 enhancer represses haematopoiesis in the lymphatic vasculature

Author: Kazenwadel, Jan, Venugopal, Parvathy, Oszmiana, Anna, Toubia, John, Arriola-Martinez, Luis, Panara, Virginia, Piltz, Sandra G., Brown, Chris, Ma, Wanshu, Schreiber, Andreas W., Koltowska, Katarzyna, Taoudi, Samir, Thomas, Paul Q., Scott, Hamish S., Harvey, Natasha L.

Issue&Volume: 2023-01-25

Abstract: Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development1,2,3. Here we describe a novel enhancer element that is important for regulating the expression of Prox1 in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. Genome editing of the enhancer to remove five nucleotides encompassing the GATA2-binding site resulted in perinatal death of homozygous mutant mice due to profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibited reduced expression of genes characteristic of lymphatic endothelial cell identity and increased expression of genes characteristic of haemogenic endothelium, and acquired the capacity to generate haematopoietic cells. These data not only reveal a transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity but also demonstrate that the lymphatic endothelium has haemogenic capacity, ordinarily repressed by Prox1.

DOI: 10.1038/s41586-022-05650-9

Source: https://www.nature.com/articles/s41586-022-05650-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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