| Autor: |
Grazia Abou-Ezzi, Teerawit Supakorndej, Jingzhu Zhang, Bryan Anthony, Joseph Krambs, Hamza Celik, Darja Karpova, Clarissa S. Craft, Daniel C. Link |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 13, Iss 1, Pp 48-60 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2019.05.017 |
| Popis: |
Summary: Mesenchymal stromal cells are key components of hematopoietic niches in the bone marrow. Here we abrogated transforming growth factor β (TGF-β) signaling in mesenchymal stem/progenitor cells (MSPCs) by deleting Tgfbr2 in mesenchymal cells using a doxycycline-repressible Sp7 (osterix)-Cre transgene. We show that loss of TGF-β signaling during fetal development results in a marked expansion of CXCL12-abundant reticular (CAR) cells and adipocytes in the bone marrow, while osteoblasts are significantly reduced. These stromal alterations are associated with significant defects in hematopoiesis, including a shift from lymphopoiesis to myelopoiesis. However, hematopoietic stem cell function is preserved. Interestingly, TGF-β signaling is dispensable for the maintenance of mesenchymal cells in the bone marrow after birth under steady-state conditions. Collectively, these data show that TGF-β plays an essential role in the lineage specification of fetal but not definitive MSPCs and is required for the establishment of normal hematopoietic niches in fetal and perinatal bone marrow. : Link and colleagues show the pivotal role of TGF-β signaling in mesenchymal cells on the emergence of hematopoietic niches in the bone marrow during fetal development. Abrogating TGF-β signaling in mesenchymal cells during development results in a marked expansion of adipocytes and CAR cells in the bone marrow, while osteoblasts are reduced. Keywords: mesenchymal stem cells, transforming growth factor β, bone marrow niche, lineage commitment, hematopoiesis, bone metabolism, adipocyte, CAR cells, and osteoblast |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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