Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

Smith-Berdan, Stephanie; Schepers, Koen; Ly, Alan; Passegué, Emmanuelle; Forsberg, Erik

doi:10.4161/cc.11.4.19146

Cited by 24 publications

(29 citation statements)

References 58 publications

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“…In the bone marrow, multiple Robo receptors are expressed in HSCs while Slit ligands are expressed in the endosteal niche, which is comprised of osteoblasts that maintain a long-term population of HSCs [60]–[62]. While the Robo4 receptor is thought to mediate proper HSC adhesion to the niche [30], [61], there is some discrepancy regarding the exact role that Robo4 plays in HSCs [63].…”

Section: Discussionmentioning

confidence: 99%

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

et al. 2014

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Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche.

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Section: Discussionmentioning

confidence: 99%

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

et al. 2014

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“…Pleiotrophin is synthesized by sinusoidal endothelial cells and Cxcl12 -expressing perivascular stromal cells and acts non-cell-autonomously to promote HSC function 115 . Robo4, a Slit receptor expressed by HSCs and endothelial cells, regulates HSC localization in the bone marrow 116,117 . The Slit2 ligand is restricted to MSCs and possibly other osteoblast lineage cells.…”

Section: Novel Niche Factorsmentioning

confidence: 99%

The bone marrow niche for haematopoietic stem cells

Morrison

Scadden

2014

Nature

1,976

1,800

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Preface Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a paradigm for understanding mammalian stem cells and their niches, yet the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Here we review progress in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum, and functional heterogeneity among perivascular microenvironments.

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“…For instance, a number of studies using fluorescent reporters or immunophenotypical signatures have indicated that in mouse BM, mesenchymal, and vascular cells account for ,1% of total mononuclear cellular pool. [31][32][33][34][35] However, by direct comparison with imaging data 14,31 ( Figure 1B) it becomes unequivocally obvious that such quantifications result in a vast underestimation of these cell types, a limitation worth taking into account when drawing conclusions on the physiological relevance of stromal subsets. …”

Section: Cellular Content Of Bm Tissues In Mice and Humansmentioning

confidence: 99%

Quantification and three-dimensional microanatomical organization of the bone marrow

Nombela‐Arrieta

Manz

2017

Blood Advances

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Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease.Since Neumann and Bizzozero independently proposed in 1868 that the origin of blood cells was to be found in soft tissues contained inside bone cavities, the bone marrow (BM) has continued to fascinate scientists and clinicians alike. 1,2 Yet more than a century later, our understanding of how the hematopoietic, immune, and bone-forming tasks of the BM are tightly controlled and integrated in the context of one common anatomical space is still incomplete. Methodological approaches and advances to study BM tissuesEarly studies on BM cellular composition and microarchitecture date back to the 19th century when the first biopsies of marrow content were performed in living individuals. 3 Microscopic observation of BM smears and examination of histological sections became the standard technique, which is still used to this day to study, diagnose, and classify hematologic disorders. The realization in the post-World War II era that transplantation of BM cells from healthy individuals could rescue the lethal effects of high-dose irradiation on hematopoiesis galvanized scientific interest in BM and lead to the development of methods to detect and measure hematopoietic stem and progenitor cell (HSPC) activity, absolute cellularity, lineage-specific half-lives, and kinetics of cell production in the BM of humans and in laboratory animals. 4,5 Gradual improvements in light and electron microscopy further refined the understanding of the quantitative composition and ultrastructural features of BM tissues. 6 The biggest leap in the fields of immunology and hematology came with the advent of recombinant antibody technology and flow cytometry in the 1960s. These breakthroughs permitted the identification, quantification, and isolation of diverse populations from highly heterogeneous cell suspensions through detection of phenotypic traits. 5 Indeed, to this day, flow cytometry remains the technological mainstay for the study and dissection of the hematopoietic system.Immunolabeling methods were further adopted in modern fluorescence-based microscopy to discriminate cellular phenotypes in tissue sections and study cellular organization in the BM. In recent years, confocal microscopy has become the most popular modality to define spatial relationships and study developmental-stage specific localization patterns, with a keen interest of many groups in the dissection of HSPC niches. 7 In addition, intravital multiphoton microscopy is employed to obtain dyna...

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Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations

Cited by 24 publications

References 58 publications

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

The bone marrow niche for haematopoietic stem cells

Quantification and three-dimensional microanatomical organization of the bone marrow

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