Multi-organ functions of yolk sac during human early development

Rachel A Botting; Issac Goh; Antony Rose; Simone Webb; Justin Engelbert; Yorick Gitton; Emily Stephenson; Mariana Quiroga Londoño; Michael Mather; Nicole Mende; Ivan Imaz-Rosshandler; Dave Horsfall; Daniela Basurto-Lozada; Nana-Jane Chipampe; Victoria Rook; Pavel Mazin; M. S. Vijayabaskar; Rebecca Hannah; Laure Gambardella; Kile Green; Stéphane J. Ballereau; Megumi Inoue; Elizabeth J. Tuck; Valentina Lorenzi; Kwasi Kwakwa; Clara Alsinet; Bayanne Olabi; Mohi Miah; Chloe Admane; Dorin-Mirel Popescu

doi:10.1101/2022.08.03.502475

Developmental BiologybioRxivAug 3, 2022

Preprint

Multi-organ functions of yolk sac during human early development

Rachel A Botting iD, Issac Goh iD, Antony Rose iD, Simone Webb iD, Justin Engelbert iD, Yorick Gitton iD, Emily Stephenson iD, Mariana Quiroga Londoño iD, Michael Mather, Nicole Mende iD, Ivan Imaz-Rosshandler, Dave Horsfall iD, Daniela Basurto-Lozada iD, Nana-Jane Chipampe iD, Victoria Rook iD, Pavel Mazin iD, M. S. Vijayabaskar iD, Rebecca Hannah iD, Laure Gambardella iD, Kile Green iD, Stéphane J. Ballereau iD, Megumi Inoue iD, Elizabeth J. Tuck iD, Valentina Lorenzi iD, Kwasi Kwakwa, , Muzlifah A. Haniffa iD

Abstract

The yolk sac (YS) represents an evolutionarily-conserved extraembryonic structure that ensures timely delivery of nutritional support and oxygen to the developing embryo. However, the YS remains ill-defined in humans. We therefore assemble a complete single cell 3D map of human YS from 3-8 post conception weeks by integrating multiomic protein and gene expression data. We reveal the YS as a site of primitive and definitive haematopoiesis including a YS-specific accelerated route to macrophage production, a source of nutritional/metabolic support and a regulator of oxygen-carrying capacity. We reconstruct the emergence of primitive haematopoietic stem and progenitor cells from YS hemogenic endothelium and their decline upon stromal support modulation as intraembryonic organs specialise to assume these functions. The YS therefore functions as three organs in one revealing a multifaceted relay of vital organismal functions as pregnancy proceeds. One Sentence SummaryHuman yolk sac is a key staging post in a relay of vital organismal functions during human pregnancy.

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