Decoding human fetal liver haematopoiesis

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.

Contact
Muzlifah Haniffa
DOI
10.1038/s41586-019-1652-y
Release
9 October 2019
Lab
Haniffa Lab
Tissue
Fetal Liver, Yolk Sac
Assay
10x 3' v2, Smart-seq2
Disease
None
Organism
Homo sapiens

scRNA-seq Datasets

Dataset
Tissue
Assay
Disease
Organism
Count
Fetal Liver
10x 3' v2
None
Homo sapiens
113063
Yolk Sac
10x 3' v2
None
Homo sapiens
10071

Smart-seq2 Datasets

Dataset
Tissue
Assay
Disease
Organism
Count
Fetal Liver
Smart-seq2
None
Homo sapiens
1206

Reproducibility

Reproducibility is a major principle underpinning the scientific method. We make publicly available the raw data and analysis scripts associated with each collection.

Human Cell Atlas

Human Cell Atlas

Developmental

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.

Read More