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Yolk sac cell atlas reveals multiorgan functions during human early development

Lookup NU author(s): Issac Goh Kai'EnORCiD, Dr Rachel Botting, Antony Rose, Dr Simone WebbORCiD, Justin Engelbert, Dr Emily StephensonORCiD, Michael Mather, Dave Horsfall, Daniela Basurto Lozada, Nana-Jane Chipampe, Dr Kile GreenORCiD, Dr Bayanne Olabi, Mohi Miah, Chloe Admane, Dr Dorin-Mirel Popescu, Dr Meghan Acres, David Dixon, Dr Steven LisgoORCiD, Professor Deborah HendersonORCiD, Dr Laura Jardine, Professor Muzlifah Haniffa

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygento the developing embryo but remains ill-defined in humans. We therefore assembled acomprehensive multiomic reference of human YS from 3-8 post-conception weeks by integratingsingle-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis,we highlight roles in metabolism, coagulation, vascular development, and hematopoieticregulation. We reconstructed the emergence and decline of YS hematopoietic stem/progenitor cellsfrom hemogenic endothelium and revealed a YS-specific accelerated route to macrophageproduction that seeds developing organs. The multiorgan functions of YS are superseded asintraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancyproceeds.One-Sentence Summary: The human yolk sac is a key staging post in a relay of vitalorganismal functions during human pregnancy.


Publication metadata

Author(s): Goh I, Botting R, Rose A, Webb S, Engelbert J, Gitton Y, Stephenson E, Quiroga Londoño M, Mather M, Mende N, Imaz-Rosshandler I, Horsfall D, Basurto-Lozada D, Chipampe N-J, Rook V, Yang L, Mazin P, Vijayabaskar MS, Ton M-L, Lee J, Keitley D, Hannah R, Gambardella L, Green K, Ballereau S, Inoue M, Tuck E, Lorenzi V, Kwakwa K, Alsinet C, Olabi B, Miah M, Admane C, Popescu D, Ness T, Acres M, Dixon D, Coulthard R, Lisgo S, Henderson D, Dann E, Suo C, Kinston S, Park J-E, Polanski K, van Dongen S, Meyer K, De Bruijn M, Palis J, Behjati S, Laurenti E, Wilson N, Marioni J, Vento-Tormo R, Chedotal A, Bayraktar O, Roberts I, Jardine L, Gottgens B, Teichmann S, Haniffa M

Publication type: Article

Publication status: Published

Journal: Science

Year: 2023

Volume: 381

Issue: 6659

Print publication date: 18/08/2023

Acceptance date: 03/07/2023

Date deposited: 18/08/2023

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science (AAAS)

URL: https://doi.org/10.1126/science.add7564

DOI: 10.1126/science.add7564

ePrints DOI: 10.57711/b3r1-6862

Notes: The human yolk sac is a key staging ground for an array of vital organismal functions during development in utero.


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Funding

Funder referenceFunder name
10104/Z/15/Z
107630/Z/15/A
108413/A/15/D
206328/Z/17/Z
215116/Z/18/ZWellcome Trust
MR/R006237/1Medical Research Council (MRC)
WT206194
WT223092/Z/21/Z
WT107931/Z/15/Z
WT211276/Z/18/Z
WT220540/Z/20/A

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