Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches

• Published in: Nature (London) 2013-03, Vol.495 (7440), p.231-235
• Main Authors: Ding, Lei, Morrison, Sean J.
• Format: Article
• Language: English
• Subjects: 631/532/2139; Animals; Blood; Bone marrow; Bone Marrow - metabolism; Cell Movement; Cellular Microenvironment; Chemokine CXCL12 - deficiency; Chemokine CXCL12 - metabolism; Endothelial Cells - metabolism; Female; Flow cytometry; Gene Knock-In Techniques; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humanities and Social Sciences; Intermediate Filament Proteins - genetics; Intermediate Filament Proteins - metabolism; letter; Lymphocytes; Lymphoid Progenitor Cells - cytology; Lymphoid Progenitor Cells - metabolism; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nestin; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Physiological aspects; Science; Spleen; Stem cells; Stromal Cells - metabolism; Transplants & implants
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11885

A study of the physiological sources of the chemokine CXCL12 in mice shows that haematopoietic stem cells occupy a perivascular niche in the bone marrow whereas early lymphoid progenitors occupy a distinct endosteal niche. Multiple stem cell niches in bone marrow The chemokine CXCL12 has an important role in maintaining haematopoietic stem cell (HSC) function. Two complementary papers in the issue of Nature study the effects of conditional deletion of Cxcl12 from candidate niche cells in the bone marrow and arrive at similar conclusions despite using different cre and Cxcl12 alleles. Lei Ding and Sean Morrison map CXCL12 expression in different (putative) niche components of the adult mouse bone marrow, showing that deletion of Cxcl12 from endothelial cells, but not Lepr – cre -targeted perivascular stromal cells, contributes to HSC maintenance. These niches do not overlap, indicating compartmentalization in the bone marrow microenvironment. Daniel Link and colleagues deleted Cxcl12 from candidate niche stromal cell populations and found that expression of CXCL12 from osterix-expressing stromal cells supports B-lymphoid progenitors and retains haematopoietic progenitor cells in the bone marrow, whereas its expression from stromal cells in the perivascular region supports HSCs. These insights into the complexity of the HSC niche are of relevance to work on the development of haematopoietic disease. Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche 1 , most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs 1 and restricted progenitors 2 , 3 reside within distinct, specialized niches or whether they share a common niche. Here we assess the physiological sources of the chemokine CXCL12 for HSC and restricted progenitor maintenance. Cxcl12 DsRed knock-in mice (DsRed-Express2 recombined into the Cxcl12 locus) showed that Cxcl12 was primarily expressed by perivascular stromal cells and, at lower levels, by endothelial cells, osteoblasts and some haematopoietic cells. Conditional deletion of Cxcl12 from haematopoietic cells or nestin– cre -expressing cells had little or no effect on HSCs or restricted progenitors. Deletion of Cxcl12 from endothelial cells depleted HSCs but not myeloerythroid or lymphoid progenitors. Deletion of Cxcl12 from perivascular stromal cells depleted HS