Distinctive Mesenchymal-Parenchymal Cell Pairings Govern B Cell Differentiation in the Bone Marrow

被引:39
|
作者
Yu, Vionnie W. C. [1 ,2 ,3 ]
Lymperi, Stefania [1 ,2 ,3 ]
Oki, Toshihiko [1 ,2 ,3 ]
Jones, Alexandra [1 ,2 ,3 ]
Swiatek, Peter [1 ,2 ,3 ]
Vasic, Radovan [1 ,2 ,3 ]
Ferraro, Francesca [1 ,2 ,3 ,4 ]
Scadden, David T. [1 ,2 ,3 ,5 ]
机构
[1] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA
[2] Harvard Stem Cell Inst, Boston, MA 02114 USA
[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA
[4] Univ Penn Hlth Syst, Penn Hosp, Dept Med, 800 Spruce St, Philadelphia, PA 19107 USA
[5] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA
来源
STEM CELL REPORTS | 2016年 / 7卷 / 02期
关键词
HEMATOPOIETIC STEM-CELL; GROWTH-FACTOR-I; OSTEOBLAST DIFFERENTIATION; NICHE; PROGENITORS; MAINTENANCE; LINEAGE; OSTERIX; MICE; IDENTIFICATION;
D O I
10.1016/j.stemcr.2016.06.009
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Bone marrow niches for hematopoietic progenitor cells are not well defined despite their critical role in blood homeostasis. We previously found that cells expressing osteocalcin, a marker of mature osteolineage cells, regulate the production of thymic-seeding T lymphoid progenitors. Here, using a selective cell deletion strategy, we demonstrate that a subset of mesenchymal cells expressing osterix, a marker of bone precursors in the adult, serve to regulate the maturation of early B lymphoid precursors by promoting pro-B to pre-B cell transition through insulin-like growth factor 1 (IGF-1) production. Loss of Osx(+) cells or Osx-specific deletion of IGF-1 led to a failure of B cell maturation and the impaired adaptive immune response. These data highlight the notion that bone marrow is a composite of specialized niches formed by pairings of specific mesenchymal cells with parenchymal stem or lineage committed progenitor cells, thereby providing distinctive functional units to regulate hematopoiesis.
引用
收藏
页码:220 / 235
页数:16
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