Long-Term Hematopoietic Stem Cells Require Stromal Cell-Derived Factor-1 for Colonizing Bone Marrow during Ontogeny

Abstract

The physiological role of SDF-1 on hematopoietic stem cells (HSCs) remains elusive. We show that colonization of bone marrow by HSCs in addition to myeloid cells is severely impaired in SDF-1(-/-) embryos by a long-term repopulation assay. Colonization of spleen by HSCs was also affected, but to a lesser extent. Enforced expression of SDF-1 under the control of vascular-specific Tie-2 regulatory sequences could completely rescue the reduction of HSCs but not myeloid cells in SDF-1(-/-) bone marrow. SDF-1 was detected in the vicinity of the vascular endothelial cells in fetal bone marrow. SDF-1 plays a critical role in colonization of bone marrow by HSCs and myeloid cells during ontogeny, and the mechanisms by which SDF-1 functions are distinct between HSCs and myeloid cells.

Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and β cell regeneration in a T1D model

“…The role of the CXCR4/SDF-1 axis in the retention of hematopoietic stem cells is well established. 42 Our data demonstrate the lack of Treg cells in correlation with the downregulation of the expression of the chemokine SDF-1 in the PLNs of the diabetic NOD mice. The resumption of euglycemia in the antea-diabetic mice is associated with the recovery of the Treg cell population in the PLNs of these animals.…”

The niche of stellate cells within rat liver #

“…18,19 The chemokine cysteine-X-cysteine receptor 4 (CXCR4) is a G proteincoupled seven-span transmembrane protein which binds SDF1 exclusively. 20,21 The SDF-1/CXCR4 axis plays an essential role in directing hematopoietic stem cells along a SDF1 gradient to their final niche in the bone marrow during ontogenesis, 22 but also in their mobilization into the peripheral blood. 23 Stem cell niches are further innervated by the sympathetic nervous system, which is involved in regulation of hematopoietic stem cell recruitment.…”

Innate immunity as orchestrator of stem cell mobilization

“…7 This colonization is regulated by a-chemokine stromal-derived factor-1 (SDF-1), a potent chemoattractant for HSPCs, that at this time is expressed by developing stroma in fetal bones, whereas its receptor CXCR4 is expressed on HSPCs. 8 As SDF-1 and CXCR4 knock-out animals exhibit normal FL hematopoiesis, but impaired colonization of BM by HSPCs, the SDF-1-CXCR4 receptor axis is crucial for BM colonization, but not for accumulation of HSPCs in FL. 9 Later on in adult life, a small percentage of HSPCs is continuously released from BM niches into peripheral blood (PB), which may be envisioned as a highway by which HSPCs can relocate between distant stem cell niches to keep the pool of BM stem cells in balance.…”