Developmental potential of hematopoietic stem cells determined using retrovirally marked allophenic marrow

Zant, Gary Van; Chen, Jau-Jiin; Scott-Micus, K.

doi:10.1182/blood.v77.4.756.756

Cited by 30 publications

(4 citation statements)

References 15 publications

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“…This possible regulatory role in limiting the number of cell divisions in HSCs warrants further investigation, for example in retroviral gene therapy protocols with HSCs as target cells. Future studies of the role of TNF in steady state hematopoiesis should include the analysis of mice older than 20 mo and the generation of allophenic mice, which would allow the tracking of HSC progeny over time, without perturbing the hematopoietic system (70).…”

Section: Discussionmentioning

confidence: 99%

Essential Role for the P55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

Rebel

Hartnett

Hill

et al. 1999

The Journal of Experimental Medicine

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Hematopoietic stem cell (HSC) self-renewal is a complicated process, and its regulatory mechanisms are poorly understood. Previous studies have identified tumor necrosis factor (TNF)-α as a pleiotropic cytokine, which, among other actions, prevents various hematopoietic progenitor cells from proliferating and differentiating in vitro. However, its role in regulating long-term repopulating HSCs in vivo has not been investigated. In this study, mice deficient for the p55 or the p75 subunit of the TNF receptor were analyzed in a variety of hematopoietic progenitor and stem cell assays. In older p55−/− mice (>6 mo), we identified significant differences in their hematopoietic system compared with age-matched p75−/− or wild-type counterparts. Increased marrow cellularity and increased numbers of myeloid and erythroid colony-forming progenitor cells (CFCs), paralleled by elevated peripheral blood cell counts, were found in p55-deficient mice. In contrast to the increased myeloid compartment, pre-B CFCs were deficient in older p55−/− mice. In addition, a fourfold decrease in the number of HSCs could be demonstrated in a competitive repopulating assay. Secondary transplantations of marrow cells from primary recipients of p55−/− marrow revealed impaired self-renewal ability of p55-deficient HSCs. These data show that, in vivo, signaling through the p55 subunit of the TNF receptor is essential for regulating hematopoiesis at the stem cell level.

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Section: Discussionmentioning

confidence: 99%

Essential Role for the P55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

Rebel

Hartnett

Hill

et al. 1999

The Journal of Experimental Medicine

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“…To this end, we estimated the maximal number of cobblestone area-forming cell (CAFC) d35 population doublings in two genetically distinct mouse strains, C57BL/6 (B6) and DBA/2 (D2) mice, which differ with respect to numerous HSC traits [17][18][19][20]. During normal aging, the number of stem cells and their repopulating ability after transplant decreased in D2 mice, whereas these parameters increased in B6 mice [17,19,[21][22][23][24][25][26][27]. Intriguingly, D2 mice have a shorter life span than B6 animals have [28].…”

Section: Introductionmentioning

confidence: 99%

Impaired Hematopoietic Stem Cell Functioning After Serial Transplantation and During Normal Aging

et al. 2005

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Adult somatic stem cells possess extensive self-renewal capacity, as their primary role is to replenish aged and functionally impaired tissues. We have previously shown that the stem cell pool in short-lived DBA/2 (D2) mice is reduced during aging, in contrast to longlived C57BL/6 (B6) mice. This suggests the existence of a genetically determined mitotic clock operating in stem cells, which possibly limits organismal aging. In the study reported here, unfractionated bone marrow (BM) cells or highly purified Lin -Sca-1 + c-kit + (LSK) cells were serially transplanted in lethally irradiated D2 and B6 mice. In both strains, serial transplantation resulted in a substantial loss of stem cell activity. However, as we estimate that in B6 mice, the maximum number of population doublings of primitive cells is approximately 30, in D2 mice this is only approximately 20, resulting in a 1,000-fold difference in expansion potential, irrespective of whether whole bone marrow or purified hematopoietic stem cells (HSCs) were transplanted. Interestingly, recipients reconstituted with serially transplanted BM cells were able to accept a freshly isolated graft without any further conditioning. Finally, we show that whereas transplantation of BM cells into healthy, nonconditioned, young B6 recipients does not lead to engraftment, young BM cells do engraft and provide multilineage reconstitution in nonirradiated aged mice. Our data clearly establish the relevance of an intrinsic, genetically controlled program associated with impaired stem cell functioning during aging. Stem Cells 2005;23:82-92

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“…There are grounds to believe that age-related changes in stem cells are reversible, because in skeletal muscle satellite cells of mouse, it was shown [ 63 ] that a rejuvenation of the satellite cells of older animals takes place during heterochronic parabiosis. Age-related changes in the HSCs of mice may also be reversible [ 64 ]. As for germinal SC, significant aging of niches where they are located was demonstrated [ 65 ].…”

Section: Aging Stem Cellsmentioning

confidence: 99%

Self-Renewalof Stem Cells

2009

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Developmental potential of hematopoietic stem cells determined using retrovirally marked allophenic marrow

Cited by 30 publications

References 15 publications

Essential Role for the P55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

Essential Role for the P55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level

Impaired Hematopoietic Stem Cell Functioning After Serial Transplantation and During Normal Aging

Self-Renewalof Stem Cells

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