EpoR-tdTomato-Cre mice enable identification of EpoR expression in subsets of tissue macrophages and hematopoietic cells
EpoR-tdTomato-Cre mice enable identification of EpoR expression in subsets of tissue macrophages and hematopoietic cells
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EpoR-tdTomato-Cre 小鼠能够鉴定组织巨噬细胞和造血细胞亚群中的 EpoR 表达
DOI：
10.1182/blood.2021011410
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发表时间：
2021-11-18
期刊：
影响因子：
20.3
通讯作者：
An, Xiuli
中科院分区：
文献类型：
--
作者：
Zhang, Huan;Wang, Shihui;An, Xiuli
传统上，促红细胞生成素受体（EpoR）被认为是一种红系特异性基因。值得注意的是，越来越多的证据表明，EpoR的表达远不止于红系细胞。然而，EpoR在非红系细胞中的表达一直存在争议。在本研究中，我们构建了EpoR - tdTomato - Cre小鼠，并利用它们来检测EpoR在组织巨噬细胞和造血细胞中的表达。我们发现，与之前可用的EpoR - eGFPcre小鼠形成鲜明对比，在后者中仅能在红系细胞中检测到非常微弱的eGFP信号，而tdTomato在所有发育阶段的胎肝（FL）和骨髓（BM）红系细胞中都很容易检测到，并且在红细胞生成过程中呈现动态变化。与我们最近的发现一致，即红系造血岛（EBI）巨噬细胞以表达EpoR为特征，tdTomato在胎肝和骨髓的EBI巨噬细胞中都很容易检测到。此外，tdTomato在骨髓中的造血干细胞、祖细胞、巨核细胞和B细胞亚群，以及脾脏红髓巨噬细胞和肝脏库普弗细胞中也能检测到。EpoR - tdTomato - Cre介导的floxed STOP序列的切除进一步证明了EpoR的表达。重要的是，促红细胞生成素（EPO）注射选择性地促进了表达EpoR的细胞的增殖，并在造血过程中诱导了红系谱系偏向。我们的研究结果表明EPO / EpoR在造血过程中具有广泛作用，值得进一步研究。EpoR - tdTomato - Cre小鼠品系为促进未来对各种非造血细胞中EpoR表达和调控的研究，以及为功能研究对表达EpoR的细胞进行条件性基因表达调控提供了有力工具。
The erythropoietin receptor (EpoR) has traditionally been thought of as an erythroid-specific gene. Notably, accumulating evidence suggests that EpoR is expressed well beyond erythroid cells. However, the expression of EpoR in non-erythroid cells has been controversial. In this study, we generated EpoR-tdTomato-Cre mice and used them to examine the expression of EpoR in tissue macrophages and hematopoietic cells. We show that in marked contrast to the previously available EpoR-eGFPcre mice, in which a very weak eGFP signal was detected in erythroid cells, tdTomato was readily detectable in both fetal liver (FL) and bone marrow (BM) erythroid cells at all developmental stages and exhibited dynamic changes during erythropoiesis. Consistent with our recent finding that erythroblastic island (EBI) macrophages are characterized by the expression of EpoR, tdTomato was readily detected in both FL and BM EBI macrophages. Moreover, tdTomato was also detected in subsets of hematopoietic stem cells, progenitors, megakaryocytes, and B cells in BM as well as in spleen red pulp macrophages and liver Kupffer cells. The expression of EpoR was further shown by the EpoR-tdTomato-Cre-mediated excision of the floxed STOP sequence. Importantly, EPO injection selectively promoted proliferation of the EpoR-expressing cells and induced erythroid lineage bias during hematopoiesis. Our findings imply broad roles for EPO/EpoR in hematopoiesis that warrant further investigation. The EpoR-tdTomato-Cre mouse line provides a powerful tool to facilitate future studies on EpoR expression and regulation in various non-hematopoietic cells and to conditionally manipulate gene expression in EpoR-expressing cells for functional studies.