Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment

Waterstrat, Amanda; Liang, Ying; Swiderski, Carol; Shelton, Brent J.; Zant, Gary Van

doi:10.1182/blood-2008-03-143370

Cited by 56 publications

(65 citation statements)

References 36 publications

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“…Aneuploid donors and their wild-type littermates expressed the CD45.2 isoform, whereas the common wild-type competitor expressed the CD45.1 isoform. We chose to use a CD45.1 common donor because previous studies had shown that CD45.1 HSCs exhibit decreased fitness when compared with CD45.2 HSCs in competition assays (Waterstrat et al 2010), thus giving the CD45.2 aneuploid donors a slight advantage in these experiments. Additionally, we used CD45.1 recipients to unambiguously quantify the contribution from aneuploid and euploid wild-type littermate donors.…”

Section: Aneuploidy Decreases Hsc Competitive Fitness In Vivomentioning

confidence: 99%

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

et al. 2016

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Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells.

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Section: Aneuploidy Decreases Hsc Competitive Fitness In Vivomentioning

confidence: 99%

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

et al. 2016

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“…Unfortunately, the WT congenic B6.SJL (CD45.1) HSPCs have an inherent disadvantage over WT C57BL/6 (CD45.2) HSPCs, with reported defects in homing efficiency, reduction in transplantable long-term hematopoietic stem cells, and a cell-intrinsic engraftment defect as demonstrated by Waterstrat et al (2010) and us ( Figure 1B). This advantage is particularly marked if C57BL/6J mice are used as recipients and is mildly attenuated when B6.SJL mice are used as recipients, suggesting that B6.SJL cells may be impaired in their ability to interact with C57BL/6J stromal cells (Waterstrat et al, 2010). This lack of competitive balance between the two putatively congenic strains has called into question the interpretation of prior results concerning the impact of modified genes and has created a conundrum for the field.…”

Section: Introductionmentioning

confidence: 98%

“…The CD45 gene is inherited within a locus that comprises almost 40 megabases and more than 300 predicted genes (Waterstrat et al, 2010 (Sacca et al, 2013). Thus, the ideal control for HSPC characterization of these new strains is a functionally equivalent C57BL/6N mouse with the minimal change in the CD45 gene to render it detectable by a CD45.1 antibody.…”

Section: Introductionmentioning

confidence: 99%

Single targeted exon mutation creates a true congenic mouse for competitive hematopoietic stem cell transplantation: the C57BL/6-CD45.1stem mouse

Mercier

Sykes

Scadden

2016

Experimental Hematology

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“…S2A). While CD45.2 hematopoietic cells have an inherent engraftment advantage [15,16], we found that the CD45.1 WT HSCs outcompeted the CD45.2 b7KO HSCs and thus, the b7KO HSCs had a significantly reduced ability to reconstitute the lymphoid and myeloid lineages as compared to competitor WT HSCs (Fig. 2E and Supplementary Fig.…”

Section: A Subset Of Hscs In the Bm Express B7 Integrinmentioning

confidence: 87%

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

Murakami

Franco

et al. 2016

Stem Cells and Development

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a4b7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed b7 integrin. These b7 + HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over b7 -HSCs. On the other hand, HSCs that lacked b7 integrin (b7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that b7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, b7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the a4b7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that b7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.

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Congenic interval of CD45/Ly-5 congenic mice contains multiple genes that may influence hematopoietic stem cell engraftment

Cited by 56 publications

References 36 publications

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

Single targeted exon mutation creates a true congenic mouse for competitive hematopoietic stem cell transplantation: the C57BL/6-CD45.1stem mouse

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1

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