Enhancement of repopulation haemopoiesis by heterozygous connexin 43 stem cells seeded on wild-type connexin 43 stroma.
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.
Rosendaal
Martin
M
Department of Anatomy & Developmental Biology, UCL, Gower St, London WC1 E6BT, UK.
Stone
Mervyn
M
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000201:enzymology; D018929:Cell Culture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004912:Erythrocytes / Q000201:enzymology; D005838:Genotype; D005956:Glucose-6-Phosphate Isomerase / Q000032:analysis; D006098:Granulocytes / Q000201:enzymology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006579:Heterozygote; D016014:Linear Models; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000201:enzymology; D013997:Time Factors
D015415:Biomarkers; D018031:Connexin 43; D005956:Glucose-6-Phosphate Isomerase