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

Haematopoiesis in the bone marrow (BM) regulates Blood and immune cell production in postnatal life. It first emerges in human BM at 11-12 post-conception weeks. However, knowledge is scarce regarding the development of fetal BM (FBM) to meet the highly specialized needs of the fetus and newborn. 

A recent review by Jardine L. et al. describes the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression.

They found that the whole Blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM facilitates rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils, and dendritic cell subsets appearing for the first time. Also, in comparison with fetal Liver (FL) at the same gestational age, FBM exhibits substantial B-lymphocyte expansion. 

They also found that the Hematopoietic progenitors from FL, FBM, and cord blood (CB) show transcriptional and functional differences causing tissue-specific identity and cellular diversification. Further, they described that various endothelial cell types form distinct vascular structures within FBM that are compartmentalized regionally. 

Lastly, they also explained selective disruption of B-lymphocyte, erythroid and myeloid development caused by cell-intrinsic differentiation bias and extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).

Jardine L, Webb S, Goh I, et al. Blood and immune development in human fetal bone marrow and Down syndrome. Nature. 2021 Oct;598(7880):327-331. DOI: 10.1038/s41586-021-03929-x.