scholarly journals Subdivision of bone marrow microenvironments: purpose built homes for haematopoietic stem cells

2012 ◽  
Vol 32 (2) ◽  
pp. 176-177 ◽  
Author(s):  
Edwin D Hawkins ◽  
Cristina Lo Celso
2016 ◽  
Author(s):  
Adam L MacLean ◽  
Maia A Smith ◽  
Juliane Liepe ◽  
Aaron Sim ◽  
Reema Khorshed ◽  
...  

AbstractThe haematopoietic stem cell (HSC) niche provides essential micro-environmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, haematopoietic dynamics are perturbed, but it is not known whether changes to the HSC-niche interaction occur as a result. We visualise HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behaviour: (i) a pattern of revisiting previously explored space, and (ii) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (i), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life-history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC-niche micro-environments following infection.Author SummaryHaematopoietic stem cells reside in the bone marrow where they are crucially maintained by an incompletely-determined set of niche factors. Recently it has been shown that chronic infection profoundly affects haematopoiesis by exhausting stem cell function, but these changes have not yet been resolved at the single cell level. Here we show that the stem cell–niche interactions triggered by infection are heterogeneous whereby cells exhibit different behavioural patterns: for some, movement is highly restricted, while others explore much larger regions of space over time. Overall, cells from infected mice display higher levels of persistence. This can be thought of as a search strategy: during infection the signals passed between stem cells and the niche may be blocked or inhibited. Resultantly, stem cells must choose to either ‘cling on’, or to leave in search of a better environment. The heterogeneity that these cells display has immediate consequences for translational therapies involving bone marrow transplant, and the effects that infection might have on these procedures.


2018 ◽  
Vol 64 ◽  
pp. S70
Author(s):  
Myriam Haltalli ◽  
Kira Glatzel ◽  
Sam Watcham ◽  
Alexander Lipien ◽  
Sara Gonzalez Anton ◽  
...  

Nature ◽  
2014 ◽  
Vol 505 (7483) ◽  
pp. 327-334 ◽  
Author(s):  
Sean J. Morrison ◽  
David T. Scadden

2004 ◽  
Vol 10 ◽  
pp. 42
Author(s):  
A. Lanfranchi ◽  
R. Verardi ◽  
E. Baggio ◽  
E. Mazzolari ◽  
F. Porta

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4200-4200
Author(s):  
Lev Silberstein ◽  
Maria Jose Sanchez ◽  
Merav Socolovsky ◽  
Gary J. Hoffman ◽  
Sandie Piltz ◽  
...  

Abstract The stem cell leukaemia (SCL) gene encodes a basic helix-loop-helix transcription factor with a critical role in normal haematopoiesis and angiogenesis. The SCL gene is normally expressed in haematopoietic stem cells, mast cells, megakaryocytes, endothelium and smooth muscle. Aberrant expression of the SCL gene leads to T-cell acute lymphoblastic leukaemia, whereas SCL−/− mice die due to the absence of haematopoiesis. Hence, temporal and spatial regulation of SCL expression is essential. Our laboratory has previously characterised a 5.5 kb enhancer located 3′ of the SCL transcription start site, which is capable of targeting expression of b-galactozidase (LacZ) reporter gene to haematopoietic stem cells in the foetal liver and the bone marrow, as well as embryonic endothelium. Subsequent experiments showed that a 641-base pair core enhancer gave an identical pattern of lacZ expression in the embryo. However, it was unclear if the same element (later referred to as +19 core enhancer) was capable of maintaining reporter gene expression into the adulthood, since no lacZ activity was observed in postnatal mice. Using a transgenic construct containing a eukaryotic reporter gene, human placental alkaline phosphatase, we show that in the haematopoietic system, the +19 core enhancer is sufficient to target foetal liver and bone marrow HSCs, as well as mast cells and megakaryocytes. In the erythroid lineage, the enhancer is active only during the earlier stages of erythropoiesis, despite high level of SCL expression throughout erythroblast maturation, suggesting that an additional element is likely to be required to maintain SCL expression. The enhancer also targets embryonic and adult endothelium, together with vascular and visceral smooth muscle. Taken together, our results demonstrate that the 641-bp +19 core enhancer is sufficient to integrate signals upstream of SCL in blood, endothelium and smooth muscle. Our data also suggest that developmental relationship between these three mesoderm-derived lineages could be defined through a common transcriptional environment, and indicate that SCL may play a wider role in mesodermal development than previously thought.


2000 ◽  
Vol 110 (2) ◽  
pp. 385-393 ◽  
Author(s):  
Yoo Hong Min ◽  
Seung Tae Lee ◽  
Kyung Mi Choi ◽  
Jee Sook Hahn ◽  
Yun Woong Ko

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