Yolk sac cell atlas reveals multiorgan functions during human early development
Issac Goh, Rachel A. Botting, Antony Rose, Simone Webb, Justin Engelbert, Yorick Gitton, Emily Stephenson, Mariana Quiroga Londoño, Michael Mather, Nicole Mende, Iván Imaz-Rosshandler, Lu Yang, Dave Horsfall, Daniela Basurto-Lozada, Nana-Jane Chipampe, Victoria Rook, Jimmy Tsz Hang Lee, Mai-Linh Ton, Daniel Keitley, Pavel Mazin, M. S. Vijayabaskar, Rebecca Hannah, Laure Gambardella, Kile Green, Stéphane Ballereau, M. Inoue, Elizabeth Tuck, Valentina Lorenzi, Kwasi Kwakwa, Clara Alsinet, Bayanne Olabi, Mohi Miah, Chloe Admane, Dorin-Mirel Popescu, Meghan Acres, David Dixon, Thomas Ness, Rowen Coulthard, Steven Lisgo, Deborah J. Henderson, Emma Dann, Chenqu Suo, Sarah Kinston, Jong-Eun Park, Krzysztof Polański, John C. Marioni, Stijn van Dongen, Kerstin B. Meyer, Marella de Bruijn, James Palis, Sam Behjati, Elisa Laurenti, Nicola K. Wilson, Roser Vento‐Tormo, Alain Chédotal, Omer Ali Bayraktar, Irene Roberts, Laura Jardine, Berthold Göttgens, Sarah A. Teichmann, Muzlifah Haniffa
Abstract
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 The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.