Lee Lydia K, Ghorbanian Yasamine, Wang Wenyuan, Wang Yanling, Kim Yeon Joo, Weissman Irving L, Inlay Matthew A, Mikkola Hanna K A
Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA.
Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology & Biochemistry at UCI, Irvine, CA 92697, USA.
Cell Rep. 2016 Nov 22;17(9):2286-2298. doi: 10.1016/j.celrep.2016.10.080.
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1 concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks the divergence between YS primitive and definitive hematopoiesis and provides a tool for targeting YS definitive hematopoiesis and FL colonization.
发育性造血的不同波峰和位点对胎儿及成人血液生成的贡献仍不清楚。在此，我们鉴定出淋巴管内皮透明质酸受体1（LYVE1）是卵黄囊（YS）内皮以及定型造血干细胞和祖细胞（HSPCs）的标志物。妊娠中期YS和卵黄静脉中的内皮细胞被Lyve1-Cre标记，而背主动脉和胎盘的内皮细胞未被标记。大多数YS HSPCs和红系-髓系祖细胞通过Lyve1-Cre谱系追踪，但原始红细胞未被追踪，这表明它们代表不同的谱系。胎儿肝脏（FL）和成人HSPCs显示出35%-40%的Lyve1-Cre标记。对循环缺陷的Ncx1概念验证胚胎的分析确定YS是Lyve1-Cre标记的HSPCs的主要来源。FL早幼红细胞标记在胚胎第（E）11.5-13.5天广泛存在，但到E16.5时降至造血干细胞（HSC）水平，这表明来自多个来源的HSCs开始负责红细胞生成。因此，Lyve1-Cre标记了YS原始造血和定型造血之间的差异，并为靶向YS定型造血和FL定植提供了一种工具。
