Decoding human fetal liver haematopoiesis

By Dorin-Mirel Popescu, R. Botting, Emily Stephenson, Kile Green, S. Webb, Laura Jardine, Emily F. Calderbank, Krzysztof Polanski, Issac Goh, Mirjana Efremova and 46 more. Nature, 2019

515 citations recorded by the source corpus.

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. Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f9b31cf91fb909e451f82ad25ed683d6efbb44d2

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Citations in the corpus

A cell atlas of human thymic development defines T cell repertoire formation (2020, background): “Because fetal liver is the main hematopoietic organ and source of hematopoietic stem cells and multipotent progenitors (HSCs/MPPs) when the thymic rudiment develops, we analyzed paired thymus and liver samples from the same fetus (44), similar to what has been described for early hematopoietic organ”
Deciphering cell–cell interactions and communication from gene expression (2020, methodology): “…to confirm protein expression, statistically significant co-occurrence of IL-33 and its receptor was validated on adjacent AT-2 cells and basophils, respectively 41 , whereas another study used imaging flow cytometry to show interaction between macrophages and liver progenitor cells 23 .”
A human cell atlas of fetal gene expression (2020, methodology): “We then coembedded the human fetal blood cells and a scRNA-seq atlas of blood cells from the fetal liver (108), using the Seurat v3 integrationmethod (FindAnchors and IntegrateData) (15) with a chosen dimensionality of 30 on the top 3000 highly variable genes with shared gene names in both datasets.”
SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data (2018, unknown): “As a final test, we apply our method to human fetal liver data [16].”