Genetic control of hematopoietic kinetics revealed by analyses of allophenic mice and stem cell suicide

Zant, Gary Van; Eldridge, Paul W.; Behringer, Richard R.; Dewey, Michael J.

doi:10.1016/0092-8674(83)90096-x

Cited by 74 publications

(49 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it has been shown that competitive repopulation capacity of HSC is maintained (25) or increases (24) in aged C57BL/6 mice, but shows an age-related decline in DBA/2 mice (25). These findings were consistent with the observation that in embryo-aggregated D2Ͻ-ϾB6 mice, DBA/2-derived hemopoiesis is eclipsed upon aging by C57BL/6-derived hemopoiesis through stem cell-intrinsic mechanisms (3,4,51). Taken together, these data suggest that stem cell function is maintained better in long-lived C57BL/6 mice than in the shorter-lived DBA/2 mice.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

The Positive Regulatory Effect of TGF-β2 on Primitive Murine Hemopoietic Stem and Progenitor Cells Is Dependent on Age, Genetic Background, and Serum Factors

Henckaerts

Langer

Orenstein

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

TGF-β is considered a negative regulator of hemopoietic stem and progenitor cells. We have previously shown that one TGF-β isoform, TGF-β2, is, in fact, a positive regulator of murine hemopoietic stem cell function in vivo. In vitro, TGF-β2, but not TGF-β1 and TGF-β3, had a biphasic dose response on the proliferation of purified lin-Sca1++kit+ (LSK) cells, with a stimulatory effect at low concentrations, which was subject to mouse strain-dependent variation. In this study we report that the stimulatory effect of TGF-β2 on the proliferation of LSK cells increases with age and after replicative stress in C57BL/6, but not in DBA/2, mice. The age-related changes in the TGF-β2 effect correlated with life span in BXD recombinant strains. The stimulatory effect of TGF-β2 on the proliferation of LSK cells requires one or more nonprotein, low m.w. factors present in fetal calf and mouse sera. The activity of this factor(s) in mouse serum increases with age. Taken together, our data suggest a role for TGF-β2 and as yet unknown serum factors in the aging of the hemopoietic stem cell compartment and possibly in organismal aging.

show abstract

Section: Discussionsupporting

confidence: 81%

“…It is still unclear how pool size, renewal, and differentiation of HSC are regulated in vivo. These functional characteristics are subject to quantitative genetic variation in inbred mouse strains (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Quantitative trait analysis is therefore an attractive approach to elucidate regulatory mechanisms for HSC in vivo.…”

mentioning

confidence: 99%

The Positive Regulatory Effect of TGF-β2 on Primitive Murine Hemopoietic Stem and Progenitor Cells Is Dependent on Age, Genetic Background, and Serum Factors

Henckaerts

Langer

Orenstein

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…[19][20][21] After 5 days of culture, the cells were counted and plated in methylcellulose assays supported by KL, IL-3, GM-CSF, erythropoietin, and neutralizing anti-TGF-␤ antibodies for the determination of CFC content. B6 and DBA/2 mice were chosen for these studies because of the known strain-dependent variation in the hematopoietic system between these 2 mouse strains [2][3][4][5][6]8,9 and because of the availability of a relatively large set of BXD RI strains together with a dense map of polymorphic markers. [24][25][26]29 Lin Ϫ Sca1 ϩϩ kit ϩ cells from B6 mice proliferated better in response to flt3L, KL, and TPO than Lin Ϫ Sca1 ϩϩ kit ϩ cells from DBA/2 mice (P ϭ .01, n ϭ 12, paired t test; Figure 2A).…”

Section: Responsiveness To Early-acting Factors and Number Of Phenotymentioning

confidence: 99%

“…Pool size and cycling activity of the stem cell compartment are under complex intrinsic genetic control in inbred mouse strains. [2][3][4][5][6][7][8] Putative stem cell pool size, as determined by the day 35 cobblestone area-forming cell assay (CAFCd35), varies widely among inbred mouse strains. 2 This was not the case for earlier appearing, and therefore more mature, CAFCd7, indicating that the gene(s) involved act on the more primitive progenitor compartment.…”

Section: Introductionmentioning

confidence: 99%

Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines

Henckaerts

Geiger

Langer

et al. 2002

Blood

Self Cite

View full text Add to dashboard Cite

Quantitative trait analysis may shed light on mechanisms regulating hematopoiesis in vivo. Strain-dependent variation existed among C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice in the responsiveness of primitive progenitor cells to the early-acting cytokines kit ligand, flt3 ligand, and thrombopoietin. A significant quantitative trait locus was found on chromosome 2 that could not be confirmed in congenic mice, however, probably because of epistasis. Because it has been shown that alleles of unknown Xlinked genes confer a selective advantage to hematopoietic stem cells in vivo in humans and in cats, we also analyzed reciprocal male D2B6F1 and B6D2F1 mice, revealing an X-linked locus regulating the responsiveness of progenitor and stem cells to early-acting factors. Among DBA/2, B6, and BXD recombinant inbred mice, correlating genetic variation was found in the absolute number and frequency of Lin ؊ Sca1 ؉؉ kit ؉ cells, which are highly enriched in hematopoietic progenitor and stem cells, and in the number of Lin ؊ Sca1 ؉؉ kit ؊ cells, a population whose biologic significance is unknown, suggesting that both populations are functionally related. Suggestive quantitative trait loci (QTLs) for the number of Lin ؊ Sca1 ؉؉ cells on chromosomes 2, 4, and 7 were confirmed in successive rounds of mapping. The locus on chromosome 2 was confirmed in congenic mice. We thus demonstrated genetic variation in the response to cytokines critical for hematopoiesis in vivo and in the pool size of cells belonging to a phenotype used to isolate essentially pure primitive progenitor and stem cells, and we identified loci that may be relevant to the regulation of hematopoiesis in steady state. (Blood. 2002;99:3947-3954)

show abstract

“…A series of classic studies established that HSCs from different genetic backgrounds show remarkable differences in cell cycle or repopulation kinetics [14][15][16]. The effect of the genetic background has most intensively been investigated in the DBA and B6 backgrounds.…”

mentioning

confidence: 99%

Genetic Influences in Mouse Spermatogonial Stem Cell Self-Renewal

Kanatsu-Shinohara

Ogonuki

Miki

et al. 2010

Journal of Reproduction and Development

View full text Add to dashboard Cite

Abstract. Spermatogonial stem cells (SSCs) are slowly dividing cells that undergo self-renewal division to support spermatogenesis. Although the effects of genetic background in stem cell self-renewal have been well studied in hematopoietic stem cells, little is known about its effect on stem cells in other self-renewing tissues, including SSCs. To examine whether genetic factors are involved in regulation of SSC self-renewal, we first studied spermatogenesis in different inbred mouse strains (C57BL/6, DBA/2, AKR, BALB/C and C3H) after chemical damage caused by busulfan. Spermatogenesis in the DBA/2 and AKR strains was relatively resistant to busulfan treatment, whereas spermatogenesis was diminished in C57BL/6 mice and nearly ablated in C3H and BALB/C mice. Serial germ cell transplantation experiments provided functional evidence that SSCs with the DBA/2 background expanded more rapidly than those with the B6 background. Finally, we also employed the Germline Stem (GS) cell culture technique to examine the self-renewal activity in vitro. Although genetic manipulation of GS cells has been limited to those from the DBA/2 background, we produced transgenic offspring of the C3H background by electroporation of GS cells with a plasmid vector. Our results underscore the importance of genetic factors in SSC self-renewal. Furthermore, application of genetic modification techniques to GS cells with non-DBA/2 backgrounds extends the potential of a SSC-based approach in male germline modification. Key words: Germ cell transplantation, Germline stem cell, Spermatogonial stem cell (J. Reprod. Dev. 56: [145][146][147][148][149][150][151][152][153] 2010) tem cells are a unique population of cells with self-renewal activity. A single stem cell can proliferate to make two stem cells (self-renewal division), one stem cell and one differentiating cell (asymmetric division) or two differentiating cells (differentiating division) [1]. The mode of stem cell replication is altered by environmental factors. For example, stem cells have the potential to regenerate an entire organ following damage by chemicals or radiation treatment. In such cases, it is thought that the number of stem cells is initially increased by self-renewing division, followed by gradual production of differentiated cells by asymmetric division. Spermatogonial stem cells (SSCs) are the only type of stem cells that have germline potential [1,2]. Like stem cells in other self-renewing tissues, SSCs can regenerate spermatogenesis after chemical treatment [3][4][5] or after germ cell transplantation [6]. SSCs migrate into empty niches to reinitiate spermatogenesis following their microinjection into seminiferous tubules. During the first several weeks, SSCs expand on the basal membrane to form patches or networks of spermatogonia, and these cells eventually produce differentiated sperm several months after transplantation [7]. However, the mechanisms by which SSCs regulate selfrenewal and differentiation remain uncertain.In 2003, we reported a culture method to exp...

show abstract

Genetic control of hematopoietic kinetics revealed by analyses of allophenic mice and stem cell suicide

Cited by 74 publications

References 16 publications

The Positive Regulatory Effect of TGF-β2 on Primitive Murine Hemopoietic Stem and Progenitor Cells Is Dependent on Age, Genetic Background, and Serum Factors

The Positive Regulatory Effect of TGF-β2 on Primitive Murine Hemopoietic Stem and Progenitor Cells Is Dependent on Age, Genetic Background, and Serum Factors

Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines

Genetic Influences in Mouse Spermatogonial Stem Cell Self-Renewal

Contact Info

Product

Resources

About