Blood and immune development in human fetal bone marrow and Down syndrome

github

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11–12 weeks after conception, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6–7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).

Contact
Muzlifah Haniffa
DOI
10.1038/s41586-021-03929-x
Release
29 September 2021
Lab
Haniffa Lab
Tissue
Cord Blood, Fetal Bone Marrow, Fetal Liver
Assay
10x 3', 10x 5', 10x ADT, 10x VDJ-BCR, 10x VDJ-TCR, Smart-seq2
Disease
None
Organism
Homo sapiens

scRNA-seq Datasets

Dataset
Tissue
Assay
Disease
Organism
Count
Fetal Bone Marrow
10x 3'
10x 5'
10x VDJ-BCR
10x VDJ-TCR
None
Homo sapiens
103228
Fetal Bone Marrow
10x 5'
None
Homo sapiens
16743
Cord Blood
Fetal Liver
Fetal Bone Marrow
10x 3'
None
Homo sapiens
27998
Cord Blood
Fetal Liver
Fetal Bone Marrow
10x ADT
None
Homo sapiens
27988
Fetal Bone Marrow
10x 3'
None
Homo sapiens
8978
Fetal Bone Marrow
10x ADT
None
Homo sapiens
8978
Fetal Bone Marrow
Smart-seq2
None
Homo sapiens
486

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.

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