Journal
NATURE
Volume 598, Issue 7880, Pages 327-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03929-x
Keywords
-
Categories
Funding
- Wellcome Human Cell Atlas Strategic Science Support [WT211276/Z/18/Z]
- MRC Human Cell Atlas
- Wellcome Human Developmental Biology Initiative - Wellcome [WT107931/Z/15/Z]
- Lister Institute for Preventive Medicine
- NIHR - Wellcome [WT206194]
- ERC
- EU FET-OPEN MRG-GRAMMAR - Wellcome [206328/Z/17/Z]
- MRC [203151/Z/16/Z]
- Blood Cancer UK
- NIHR Oxford Biomedical Centre Research Fund - Wellcome Trust Clinical Research Career Development Fellowship [216632/Z/19/Z]
- NIHR Oxford Biomedical Centre Research Fund - NIHR Academic Clinical Lectureship
- Barbour Foundation - Action Medical Research Clinical Fellowship [GN2779]
- Royal Society [107630/Z/15/Z]
- BBSRC [BB/P002293/1]
- Wellcome Trust [MR/R006237/1]
- BBSRC [BB/P002293/1] Funding Source: UKRI
- MRC [MR/W014556/1, MR/S036113/1] Funding Source: UKRI
Ask authors/readers for more resources
Research demonstrates that the full blood and immune cell repertoire in fetal bone marrow is established within a short 6-7 week period in early second trimester, promoting rapid and extensive diversification of myeloid cells, with distinct differences from fetal liver.
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(1,2), 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).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available