Blood and immune development in human fetal bone marrow and Down syndrome
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 conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and...
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147060 |
| _version_ | 1811072957769842688 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | 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 conception1,2, 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). |
| first_indexed | 2024-09-23T09:24:28Z |
| format | Article |
| id | mit-1721.1/147060 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:24:28Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1470602023-01-12T03:41:56Z Blood and immune development in human fetal bone marrow and Down syndrome Regev, Aviv Massachusetts Institute of Technology. Department of Biology 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 conception1,2, 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). 2023-01-11T17:14:55Z 2023-01-11T17:14:55Z 2021 2023-01-11T16:57:27Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147060 Regev, Aviv. 2021. "Blood and immune development in human fetal bone marrow and Down syndrome." Nature, 598 (7880). en 10.1038/S41586-021-03929-X Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Regev, Aviv Blood and immune development in human fetal bone marrow and Down syndrome |
| title | Blood and immune development in human fetal bone marrow and Down syndrome |
| title_full | Blood and immune development in human fetal bone marrow and Down syndrome |
| title_fullStr | Blood and immune development in human fetal bone marrow and Down syndrome |
| title_full_unstemmed | Blood and immune development in human fetal bone marrow and Down syndrome |
| title_short | Blood and immune development in human fetal bone marrow and Down syndrome |
| title_sort | blood and immune development in human fetal bone marrow and down syndrome |
| url | https://hdl.handle.net/1721.1/147060 |
| work_keys_str_mv | AT regevaviv bloodandimmunedevelopmentinhumanfetalbonemarrowanddownsyndrome |