Hematopoietic capacity of connexin43 wild-type and knock-out fetal liver cells not different on wild-type stroma

Rosendaal, Martin; Jopling, Chris

doi:10.1182/blood-2002-07-2028

Cited by 9 publications

(8 citation statements)

References 21 publications

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“…Rosendaal and Jopling [23] have presented the same data, and reported no consistent difference betweeen dWT and dKO genotypes. However, the most remarkable and unexpected feature of the data is the competitive advantage of the HZ graft in the the long-term subexperiments -'unexpected' because, for single-influence (unipolar) biological processes, an effect of heterozygosity is usually intermediate between those of the WT and KO genotypes.…”

Section: Why Does Heterozygosity Win the Race For Long-term Repopulatsupporting

confidence: 58%

Enhancement of repopulation haemopoiesis by heterozygous connexin 43 stem cells seeded on wild-type connexin 43 stroma

Rosendaal

Stone²

2003

Clinical Science

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The present paper analyses the results of competitive blood-cell repopulation experiments in which Cx43-WT (connexin 43 wild-type) host mice, whose own HSCs (haemopoietic stem cells) were deleted, were grafted with fetal liver cells: 50% Gpi-1a (glucose phosphate isomerase-1a)/Cx43-WT cells competing with 50% Gpi-1b/Cx43-WT, 50% Gpi-1b/Cx43-HZ (heterozygous) or 50% Gpi-1b/Cx43-KO (knock-out) cells. The percentages of platelets, granulocytes, red cells, B-cells and T-cells containing Gpi-1b in blood samples obtained from 22 to 186 days after grafting, and the percentages of high-proliferation-potential colony-forming cells containing Gpi-1b at 255 days after grafting, were measured. The results show that, if we wait 4 months so that we measure the percentages of Gpi-1b end-cells formed by initially resting stem cells in the graft, values in HZ mice are greater than those in WT and KO mice by 10% or more. We propose a bipolar influence model for blood formation by grafted HSCs to explain this difference and other features of the data. Influence A is a direct one: for individual HSCs, the combined effect on HSC niching and HSC proliferation of Cx43 is superior to that of the KO allele. Influence B is a demographic one: HZ foundation mice compensate by having more HSCs than WT mice. The net outcome of influences A and B is that HZ is the winner.

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Section: Why Does Heterozygosity Win the Race For Long-term Repopulatsupporting

confidence: 58%

Enhancement of repopulation haemopoiesis by heterozygous connexin 43 stem cells seeded on wild-type connexin 43 stroma

Rosendaal

Stone²

2003

Clinical Science

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“…Dye transfer incidence was also detected in DCs subjected to different stimuli for different periods of time (5,15,20,24, and 28 h) (Fig. 1C).…”

Section: Mcl/tnf-␣ Stimulation Induces Gjic In Hdcsmentioning

confidence: 83%

“…GJ establish pathways of intercellular communication that coordinate processes such as embryogenesis, development, hemopoiesis, growth, and cellular response to injury (22,24,25). Individual or combinations of Cx are distributed in cell type-specific patterns, often carrying out specialized functions.…”

Section: Discussionmentioning

confidence: 99%

Functional Gap Junctions Facilitate Melanoma Antigen Transfer and Cross-Presentation between Human Dendritic Cells

Mendoza-Naranjo

Saéz

Johansson³

et al. 2007

The Journal of Immunology

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Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-α (MCL/TNF) acquire a mature phenotype in vitro and are able to trigger tumor-specific immune responses when they are used in melanoma immunotherapy in patients. In this study, we describe that MCL/TNF induces gap junction (GJ)-mediated intercellular communications and promotes melanoma Ag transfer between ex vivo produced hDCs from melanoma patients. hDCs also exhibit increased expression of the GJ-related protein connexin 43, which contributes to GJ plaque formation after MCL/TNF stimulation. The addition of GJ inhibitors suppresses intercellular tumor Ag transfer between hDCs, thus reducing melanoma-specific T cell activation. In summary, we demonstrate that MCL/TNF-stimulated hDCs can establish functional GJ channels that participate in melanoma Ag transfer, facilitating Ag cross-presentation and an effective dendritic cell-mediated melanoma-specific T cell response. These results suggest that GJs formed between hDCs used in cancer vaccination protocols could be essentials for the establishment of a more efficient antitumor response.

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“…It has been hypothesized that gap junctions participate in hematopoiesis, and therefore, they may also play a role in leukemia (387,497). However, Cx43-mediated communication between stromal and hematopoietic stem cells may not be an absolute requirement (496).…”

Section: Immune Systemmentioning

confidence: 99%

Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

Sáez

Berthoud

Brañes

et al. 2003

Physiological Reviews

1,048

952

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Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.

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Hematopoietic capacity of connexin43 wild-type and knock-out fetal liver cells not different on wild-type stroma

Cited by 9 publications

References 21 publications

Enhancement of repopulation haemopoiesis by heterozygous connexin 43 stem cells seeded on wild-type connexin 43 stroma

Enhancement of repopulation haemopoiesis by heterozygous connexin 43 stem cells seeded on wild-type connexin 43 stroma

Functional Gap Junctions Facilitate Melanoma Antigen Transfer and Cross-Presentation between Human Dendritic Cells

Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions

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