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

By Lei Ding, S. Morrison. Nature, 2013

1,223 citations recorded by the source corpus.

Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche, most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs and restricted progenitors 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. Cxcl12DsRed 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 HSCs and certain restricted progenitors and mobilized these cells into circulation. Deletion of Cxcl12 from osteoblasts depleted certain early lymphoid progenitors but not HSCs or myeloerythroid progenitors, and did not mobilize these cells into circulation. Different stem and progenitor cells thus reside in distinct cellular niches in bone marrow: HSCs occupy a perivascular niche and early lymphoid progenitors occupy an endosteal niche.

Subfields: Hematology, Immunology

View Paper: https://www.semanticscholar.org/paper/f28c31a96f829389d58abe479fb37d4eea77f101

How researchers see this paper

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In Hematology

1. S. Morrison
2. P. Frenette
3. W. Nauseef
4. N. Borregaard
5. Sandra Pinho
6. Lei Ding

In Immunology

1. N. Borregaard
2. P. Frenette
3. S. Morrison
4. W. Nauseef
5. Arturo Zychlinsky
6. C. Rosales
7. V. Papayannopoulos
8. C. Winterbourn

Citations in the corpus

• Rhythmic modulation of the hematopoietic niche through neutrophil clearance (2013, neutral): “Although at present we do not know whether and how these signals may integrate, it is possible that they cooperate for the homeostatic mobilization of HPC.”
• Neutrophils at work (2014, background): “(1) or to DCs or DC-like cells (2); they inhibit the proliferation of T cells”
• Arteriolar niches maintain haematopoietic stem cell quiescence (2013, positive): “In keeping with the notion that multiple niche constituents exert distinct functions, conditional deletion of Cxcl12 by Lepr-cre does not affect HSC number in the BM, but induces their mobilization 42 .”
• SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors (2013, background): “Conditional deletion of Scf or Cxcl12 from osteoblasts did not affect HSC frequency or function (Ding et al., 2012; Greenbaum et al., 2013; Ding and Morrison, 2013).”
• Leptin Receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow (2014, neutral): “, 2012), Cxcl12-DsRed (Ding and Morrison, 2013), Ubc-creER (Ruzankina et al.”