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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
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 The multiorgan functions of YS are superseded asintraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancyproceeds.One-Sentence Summary: The human yolk sac is a key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.
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
Data Access Statement: All raw sequencing data from this study are made publicly available at ArrayExpress as FASTQs and count matrices as follows: (i) human EL and YS 10X scRNA-seq, (ii) human embryonic YS 10X scRNA-seq, (iii) human embryonic YS Smart-seq2 scRNA-seq, (iv) human embryonic YS CITE-seq, (v) human EL CITE-seq, and (vi) human fetal liver CITE-seq. Accessions for published data reused in this study are detailed comprehensively in data S6. Processed single-cell datasets are available for interactive exploration and download as well as corresponding trained scVI and LR models via our interactive web portal (https://developmental.cellatlas.io/yolk-sac). Note, data on portals are best used for rapid visualization. For formal analysis and all code for reproducibility, including trained scVI VAE, ldVAE, and trained LR models, we recommended following our archived code available on Github and our interactive web portal. All raw and processed imaging data are available on the EBI BioImage Archive.
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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