Faculty Collaboration Database

Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration. Cell Stem Cell 2018 Sep 06;23(3):370-381.e5

Date

08/14/2018

Pubmed ID

30100167

Pubmed Central ID

PMC6482945

DOI

10.1016/j.stem.2018.07.003

Scopus ID

2-s2.0-85056484773 (requires institutional sign-in at Scopus site)   87 Citations

Abstract

Bone marrow (BM) perivascular stromal cells and vascular endothelial cells (ECs) are essential for hematopoietic stem cell (HSC) maintenance, but the roles of distinct niche compartments during HSC regeneration are less understood. Here we show that Leptin receptor-expressing (LepR+) BM stromal cells and ECs dichotomously regulate HSC maintenance and regeneration via secretion of pleiotrophin (PTN). BM stromal cells are the key source of PTN during steady-state hematopoiesis because its deletion from stromal cells, but not hematopoietic cells, osteoblasts, or ECs, depletes the HSC pool. Following myelosuppressive irradiation, PTN expression is increased in bone marrow endothelial cells (BMECs), and PTN⁺ ECs are more frequent in the niche. Moreover, deleting Ptn from ECs impairs HSC regeneration whereas Ptn deletion from BM stromal cells does not. These findings reveal dichotomous and complementary regulation of HSC maintenance and regeneration by BM stromal cells and ECs.

Author List

Himburg HA, Termini CM, Schlussel L, Kan J, Li M, Zhao L, Fang T, Sasine JP, Chang VY, Chute JP

Author

Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow
Carrier Proteins
Cell Self Renewal
Cytokines
Female
Hematopoietic Stem Cells
Male
Mice
Mice, Inbred C57BL