title: LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the Primitive Erythroid Lineage.
abstract: 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.
authors.affiliation: Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Lydia K
authors.initials: LK
authors.lastname: Lee
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology & Biochemistry at UCI, Irvine, CA 92697, USA.
authors.forename: Yasamine
authors.initials: Y
authors.lastname: Ghorbanian
authors.affiliation: Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Institute of Stem Cell Biology and Regenerative Medicine and Ludwig Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology & Biochemistry at UCI, Irvine, CA 92697, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Inlay
authors.affiliation: Department of Molecular, Cell & Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. Electronic address: hmikkola@mcdb.ucla.edu.
authors.forename: Hanna K A
authors.initials: HKA
authors.lastname: Mikkola
mesh_terms: D000375:Aging; D000818:Animals; D019070:Cell Lineage; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis; D005260:Female; D005333:Fetus / Q000166:cytology; D017353:Gene Deletion; D055018:Hemangioblasts / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D008099:Liver / Q000196:embryology; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D015017:Yolk Sac / Q000378:metabolism*; D026901:Membrane Transport Proteins
chemical_list: D019426:Integrases; D033921:Vesicular Transport Proteins; C045073:Cre recombinase; C492273:LYVE1 protein, mouse; D026901:Membrane Transport Proteins
keywords: LYVE1; definitive hematopoiesis; fetal liver; hemogenic endothelium; lineage tracing; primitive hematopoiesis; yolk sac