Lineage tracing using Wnt2b-2A-CreERT2 knock-in mice reveals the contributions of Wnt2b-expressing cells to novel subpopulations of mesothelial/epicardial cell lineages during mouse development

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Masanori Takahashi, Takayuki Isagawa, Tatsuyuki Sato, Norihiko Takeda, Kiyoshi Kawakami
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Abstract

Mesothelial and epicardial cells give rise to various types of mesenchymal cells via epithelial (mesothelial)-to-mesenchymal transition during development. However, the genes controlling the differentiation and diversification of mesothelial/epicardial cells remain unclear. Here, we examined Wnt2b expression in the embryonic mesothelium and epicardium and performed lineage tracing of Wnt2b-expressing cells by using novel Wnt2b-2A-CreERT2 knock-in and LacZ-reporter mice. Wnt2b was expressed in mesothelial cells covering visceral organs, but the expression was restricted in their subpopulations. Wnt2b-expressing cells labeled at embryonic day (E) 10.5 were distributed to the mesothelium and mesenchyme in the lungs, abdominal wall, stomach, and spleen in Wnt2b2A-CreERT2/+;R26RLacZ/+ mice at E13.0. Wnt2b was initially expressed in the proepicardial organ (PEO) at E9.5 and then in the epicardium after E10.0. Wnt2b-expressing PEO cells labeled at E9.5 differentiated into a small fraction of cardiac fibroblasts and preferentially localized at the left side of the postnatal heart. LacZ+ epicardium-derived cells labeled at E10.5 differentiated into a small fraction of fibroblasts and smooth muscle cells in the postnatal heart. Taken together, our results reveal novel subpopulations of PEO and mesothelial/epicardial cells that are distinguishable by Wnt2b expression and elucidate the unique contribution of Wnt2b-expressing PEO and epicardial cells to the postnatal heart.

Abstract Image

利用 Wnt2b-2A-CreERT2 基因敲入小鼠进行系谱追踪,揭示了小鼠发育过程中 Wnt2b 表达细胞对间皮细胞/心包细胞系新亚群的贡献。
在发育过程中,间皮细胞和心外膜细胞通过上皮(间皮细胞)向间充质细胞的转变产生各种类型的间充质细胞。然而,控制间皮细胞/心外膜细胞分化和多样化的基因仍不清楚。在这里,我们研究了Wnt2b在胚胎间皮细胞和心外膜中的表达,并利用新型Wnt2b-2A-CreERT2基因敲入小鼠和LacZ报告小鼠对表达Wnt2b的细胞进行了系谱追踪。Wnt2b在覆盖内脏器官的间皮细胞中表达,但在其亚群中表达受限。在胚胎第(E)10.5天标记的Wnt2b表达细胞分布于Wnt2b2A-CreERT2/+;R26RLacZ/+小鼠的肺、腹壁、胃和脾的间皮细胞和间充质。Wnt2b最初在E9.5期的前心外膜器官(PEO)中表达,然后在E10.0期后在心外膜中表达。E9.5时标记的Wnt2b表达的PEO细胞分化成一小部分心脏成纤维细胞,并优先定位在出生后心脏的左侧。E10.5时标记的LacZ+心外膜衍生细胞在出生后的心脏中分化为一小部分成纤维细胞和平滑肌细胞。总之,我们的研究结果揭示了可通过Wnt2b表达加以区分的PEO和间皮细胞/心外膜细胞的新亚群,并阐明了表达Wnt2b的PEO和心外膜细胞对出生后心脏的独特贡献。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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