Multi-organ functions of yolk sac during human early development

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.

Contact
Muzlifah Haniffa
Release
3 March 2022
Lab
Haniffa Lab
Tissue
AGM, Bone Marrow, Bone marrow, Brain, Embryonic Liver, Gonads, Liver, Mouse Yolk Sac, Skin, Yolk Sac, iPSC, iPSC (Definitive)
Assay
10x 3', 10x 5', CITE-seq
Disease
None
Organism
Homo sapiens, Homo sapiens_iPSC, Mus musculus

scRNA-seq Datasets

Dataset
Tissue
Assay
Disease
Organism
Count
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
169798
AGM
Bone marrow
Liver
Skin
iPSC
iPSC (Definitive)
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
5008
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
3389
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
6291
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
2262
Embryonic Liver
10x 5'
None
Homo sapiens
49376
Embryonic Liver
Yolk Sac
10x 3'
10x 5'
None
Homo sapiens
134765
Mouse Yolk Sac
10x 5'
None
Mus musculus
4717
iPSC (Definitive)
10x 3'
None
Homo sapiens_iPSC
552

CITE-seq Datasets

Dataset
Tissue
Assay
Disease
Organism
Count
Yolk Sac
CITE-seq
None
Homo sapiens
3559
Yolk Sac
CITE-seq
None
Homo sapiens
3559
Yolk Sac
CITE-seq
None
Homo sapiens
4061
Embryonic Liver
CITE-seq
None
Homo sapiens
7739
Embryonic Liver
CITE-seq
None
Homo sapiens
7739
Embryonic Liver
CITE-seq
None
Homo sapiens
9679

Supplementary Downloads

Name
Size

Supplementary tables

Supplementary tables containing supplementary data for our manuscript Multi-organ functions of yolk sac during human early development including annotations, statistical results, differentially expressed genes and logistic regression probabilities.
526.9 MB

microglia_LR_model_YS_brain_20220404.sav

Celltypist compatible logistic regression model trained between combined low-dimensional LDVAE latent representations of our YS dataset integrated with the Eze etal fetal Brain data (https://doi.org/10.1038/s41593-020-00794-1) and used for classification harmonisation between datasets
3.3 MB

microglia_LR_model_YS_skin_20220404.sav

Celltypist compatible logistic regression model trained between combined low-dimensional LDVAE latent representations of our YS dataset integrated with the Suo etal fetal Skin data (https://doi.org/10.1101/2022.01.17.476665) and used for classification harmonisation between datasets
3.9 MB

gonad_model_20220617.sav

Celltypist compatible logistic regression model trained between combined low-dimensional LDVAE latent representations of our YS dataset integrated with the Luz etal fetal Gonads data (https://doi.org/10.1038/s41586-022-04918-4) and used for classification harmonisation between datasets
10.3 KB

EC_liver_model.sav

Celltypist compatible logistic regression model trained between combined low-dimensional LDVAE latent representations of our YS dataset integrated with our matched liver single cell scRNA-seq data and used for classification harmonisation between datasets
2.2 KB

EC_FBM_model.sav

Celltypist compatible logistic regression model trained between combined low-dimensional LDVAE latent representations of our YS dataset integrated with the Jardine etal Fetal Bone marrow data (https://doi.org/10.1038/s41586-021-03929-x) and used for classification harmonisation between datasets
2.2 KB

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Reproducibility

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Human Cell Atlas

Human Cell Atlas

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The Human Developmental Cell Atlas (HDCA) aims to generate a comprehensive profile of cell types and states present during development. This detailed study of development will be critical for understanding congenital and childhood disorders, as well as ageing.

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