Format

Send to

Choose Destination
Stem Cell Reports. 2016 Aug 9;7(2):220-35. doi: 10.1016/j.stemcr.2016.06.009. Epub 2016 Jul 21.

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

Author information

1
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA.
2
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA; Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Health System, 800 Spruce Street, Philadelphia, PA 19107, USA. Electronic address: f.ferraro.mgh@gmail.com.
3
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, MA 02115, USA. Electronic address: david_scadden@harvard.edu.

Abstract

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.

PMID:
27453006
PMCID:
PMC4982987
DOI:
10.1016/j.stemcr.2016.06.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center