Yolk sac cell atlas reveals multiorgan functions during human early development

• Published in: Science (American Association for the Advancement of Science) Vol. 381; no. 6659; p. eadd7564
• Main Authors: Goh, Issac, Botting, Rachel A, Rose, Antony, Webb, Simone, Engelbert, Justin, Gitton, Yorick, Stephenson, Emily, Quiroga Londoño, Mariana, Mather, Michael, Mende, Nicole, Imaz-Rosshandler, Ivan, Yang, Lu, Horsfall, Dave, Basurto-Lozada, Daniela, Chipampe, Nana-Jane, Rook, Victoria, Lee, Jimmy Tsz Hang, Ton, Mai-Linh, Keitley, Daniel, Mazin, Pavel, Vijayabaskar, M S, Hannah, Rebecca, Gambardella, Laure, Green, Kile, Ballereau, Stephane, Inoue, Megumi, Tuck, Elizabeth, Lorenzi, Valentina, Kwakwa, Kwasi, Alsinet, Clara, Olabi, Bayanne, Miah, Mohi, Admane, Chloe, Popescu, Dorin-Mirel, Acres, Meghan, Dixon, David, Ness, Thomas, Coulthard, Rowen, Lisgo, Steven, Henderson, Deborah J, Dann, Emma, Suo, Chenqu, Kinston, Sarah J, Park, Jong-Eun, Polanski, Krzysztof, Marioni, John, van Dongen, Stijn, Meyer, Kerstin B, de Bruijn, Marella, Palis, James, Behjati, Sam, Laurenti, Elisa, Wilson, Nicola K, Vento-Tormo, Roser, Chédotal, Alain, Bayraktar, Omer, Roberts, Irene, Jardine, Laura, Göttgens, Berthold, Teichmann, Sarah A, Haniffa, Muzlifah
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 18.08.2023; American Association for the Advancement of Science (AAAS)
• Subjects: Aorta; Atlases as Topic; Blood; Blood Coagulation - genetics; Cell culture; Coagulation; Differentiation (biology); Embryonic Development - genetics; Embryos; Endoderm; Endothelium; Epitopes; Erythropoiesis; Erythropoietin; Female; Fluorescence microscopy; Gene Expression; Gene Expression Profiling; Gene sequencing; Growth factors; Hematopoiesis; Hematopoiesis - genetics; Hematopoietic stem cells; Hemoglobin; Hemopoiesis; Human performance; Humans; Hybridization; Imaging techniques; Immune system; Individualized Instruction; Interrogation; Life Sciences; Light sheets; Liver; Liver - embryology; Macrophages; Metabolism; Microglia; Monocytes; Pluripotency; Pregnancy; Proteins; Rabbits; Stem cells; Thrombopoietin; Tissue analysis; Tissue engineering; Yolk; Yolk sac; Yolk Sac - cytology; Yolk Sac - metabolism
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.add7564

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.