Age and stage dependency of estrogen receptor expression by lymphocyte precursors

Igarashi, Hideya; Kouro, Taku; Yokota, Takafumi; Comp, Phillip C.; Kincade, Paul W.

doi:10.1073/pnas.011513098

Cited by 148 publications

(95 citation statements)

References 52 publications

(35 reference statements)

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“…However, the expression of receptors, such as estrogen and progesterone receptor, varies during ontogeny. 4 Consistent with murine studies, adult human BM, and not CB CD34 ϩ , expresses detectable levels of estrogen and progesterone, whereas androgen receptor is expressed in both. 4 Although further experiments are required to identify sex-specific mechanisms of HSC engraftment, our study has revealed their key role and supports the concept of recipient sex as a critical variable in the context of stem cell transplantation studies.…”

Section: Sex-dependent Engraftment Of Human Hscs 3705supporting

confidence: 58%

“…Interestingly, sex-associated hormones, including androgens and estrogen, have been directly implicated in regulating hematopoietic cell function. [2][3][4] During the course of our functional analyses of HSCs using the recently developed NOD/SCID/ IL-2Rg c -null (NSG) mice, 5 we observed that the recipient sex plays a critical role in the engraftment and proliferation of human HSCs. Specifically, female NSG mice are far superior to their male counterparts in engrafting and detection of single human HSCs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients

Notta

Doulatov

Dick

2010

Blood

111

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Repopulation of immunodeficient mice remains the primary method to assay human hematopoietic stem cells (HSCs). Here we report that female NOD/SCID/IL-2Rg c -null mice are far superior in detecting human HSCs (Lin ؊ CD34 ؉ CD38 ؊ CD90 ؉ CD45RA ؊ ) compared with male recipients. When multiple HSCs were transplanted, female recipients displayed a trend (1.4-fold) toward higher levels of human chimerism (female vs male: injected femur, 44.4 ؎ 9.3 vs 32.2 ؎ 6.2; n ‫؍‬ 12 females, n ‫؍‬ 24 males; P ‫؍‬ .1). IntroductionThe dynamic interplay between donor hematopoietic stem cells (HSCs) and the recipient microenvironment governs the survival and proliferation of HSCs in a transplantation setting. A complex network of cells within the microenvironment regulates HSC function via direct interaction or secretion of cytokines that act in an autocrine or paracrine manner. 1 However, the effects on HSCs by molecules that communicate in an endocrine fashion, such as steroid hormones, remain understudied. Interestingly, sex-associated hormones, including androgens and estrogen, have been directly implicated in regulating hematopoietic cell function. [2][3][4] During the course of our functional analyses of HSCs using the recently developed NOD/SCID/ IL-2Rg c -null (NSG) mice, 5 we observed that the recipient sex plays a critical role in the engraftment and proliferation of human HSCs. Specifically, female NSG mice are far superior to their male counterparts in engrafting and detection of single human HSCs. Methods Collection of human CBHuman cord blood (CB) was collected according to guidelines established by Trillium Health Center and University Health Network. Mononuclear cells from pooled CBs were harvested using a Ficoll gradient and subsequently depleted of mature cells (Lin Ϫ ) via negative selection using StemSep system (StemCell Technologies). Cells were viably frozen in 10% dimethyl sulfoxide solution and stored at Ϫ80°C or Ϫ150°C. Fluorescence-activated cell sortingFreshly thawed Lin Ϫ CB was stained with CD34 allophycocyanin, CD38 PC7, CD45RA fluorescein isothiocyanate, and CD90 phycoerythrin in phosphate-buffered saline plus 5% fetal calf serum at a concentration of 10 7 cells/mL for 30 minutes at 4°C. Cells were sorted on FACSAria II (BD Biosciences), and purities of more than 99% were commonly achieved in postsort analysis (data not shown). Cells were counted in Trypan blue before transplantation and resuspended in 25 L of Iscove modified Dulbecco medium/mouse in a 28.5-gauge 0.5-mL insulin syringe. Xenotransplantation and detection of human chimerismAll animal experiments were performed with the approval of the Animal Care Committee at the University Health Network. Ten-to 12-week-old NSG mice were sublethally irradiated (200-225 cGy) 24 hours before transplantation. Cells were transplanted intrafemorally as previously described. 6 Briefly, a 27-gauge needle was used to drill a hole in the right femur, which was followed by injection of cells using a 28.5-gauge insulin syringe. Mice were killed 16 to 20 weeks ...

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Section: Sex-dependent Engraftment Of Human Hscs 3705supporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients

Notta

Doulatov

Dick

2010

Blood

111

View full text Add to dashboard Cite

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“…Although our results did not reveal any significant differences between hematopoietic stem cells from early and late FL compared with adult BM, they do not exclude presence of differences like those described by Kincade et al [32,33], who demonstrated that progenitor cells belonging to the B lymphopoiesis and derived from FL cells are deficient in functional estrogen receptors [32] and also differ in other respects [33] from those of the adult BM.…”

Section: Discussioncontrasting

confidence: 48%

Early Fetal Liver Readily Repopulates B Lymphopoiesis in Adult Bone Marrow

et al. 2005

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Fetal liver (FL) becomes a major organ of hematopoiesis at mouse embryonic day (E) 11 and E12, when definitive hematopoietic stem cells, originating from the aorta-gonads-mesonephros region, colonize the hepatic tissue. Unipotent B-cell progenitors are very rare in FL by day 12, whereas erythropoiesis prevails. We have studied hematopoiesis in FL from different gestational ages, with special emphasis on B lymphopoiesis. The mRNA levels of selected liver-specific genes, hematopoietic lineage-specific genes, and genes for selected cytokines/hormones as well as for their receptors were evaluated by real-time polymerase chain reaction in FL from E12.5, E14.5, and E17.5, adult liver and adult bone marrow (BM). The level of B lineage-related gene expression in FL was very low at E12.5. There was also a significantly lower fraction of B220 + and CD19 + B cells in E12.5 FL compared with E17.5 FL. To analyze whether these differences reflect different stem cell potentials occurring during FL development, 10 6 or 5 × 10 6 of FL cells collected from embryos at E12.5 or E17.5 and those from adult BM were transplanted into sublethally irradiated (3-or 6-Gy) congenic mice. Short-term and long-term repopulation of B and T cells and granulocyte/macrophage lineages from donor FL or adult BM cells were evaluated in competition to adult hematopoiesis of sublethally irradiated recipients. In short-term repopulation, the transplantation of E12.5 FL cells resulted in a lower blood chimerism compared with that of E17.5 FL cells. However, the proportion of B lymphopoiesis exerted by E12.5 FL cells was not different from that of E17.5 FL or adult BM. This study demonstrates that E12.5 FL contains hematopoietic stem cells with fully developed B-cell repopulating capacity and that the developmental period of fetal hematopoiesis between E12.5 and E17.5 is not an obligatory phase for the adult B lymphopoiesis.

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“…We previously found that estrogen and androgen receptors are down-regulated as cells progress from Lin Ϫ c-kit Hi through Lin Ϫ c-kit Lo and subsequent stages of B-lineage differentiation. 53 Consequently, estrogen has no direct influence on CD19 ϩ precursors in bone marrow. 54 It now appears that maturing NK-lineage precursors also become hormone insensitive, beginning at the Lin Ϫ c-kit Lo stage.…”

Section: Discussionmentioning

confidence: 99%

Relationships between early B- and NK-lineage lymphocyte precursors in bone marrow

Kouro

Kumar

Kincade

2002

Blood

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IntroductionNatural killer (NK) cells have long been recognized for their importance in innate immunity, viral defense, and tumor surveillance. 1 Additionally, NK cells represent barriers to bone marrow transplantation and produce cytokines that influence other cellular components of the immune system. Impressive progress has recently been made in understanding how NK cells recognize targets for cytolytic destruction while sparing normal cells. 2 For example, it is now clear that self-tolerance of NK cells is maintained by inhibitory receptors, which are expressed on NK cells and recognize major histocompatibility complex (MHC) class I molecules. In mice, the Ly49 receptor family recognizes classical MHC I molecules, whereas the CD94/NKG2 receptors recognize the nonclassical Qa-1 b MHC I molecule. Some additional NK molecules have been suggested to function as activating receptors. 3 Recent reports suggest that the self-recognizing NK-cell receptor repertoire is built in successive fashion following contact of NK-cell precursors with environmental class I MHC molecules during development. 3,4 However, many questions remain about the origin and lifespans of NK cells. Although still incomplete, a differentiation sequence is emerging that will eventually describe how hematopoietic stem cells generate NK cells in mice and humans. 5 Although cells with NK-lineage potential can be found among undifferentiated thymocytes, and some properties are shared with T cells, the thymus is probably not the most important site for production of NK cells. 6,7 The present study was designed to obtain more precise information about relationships between early NK-lineage precursors and those of other lymphoid lineages within bone marrow.The NK-1.1 antigen encoded by the NKR P1C gene provides a useful NK-cell marker in selected strains of mice, but is also expressed on a subset of T cells (NK T cells). The DX5 antigen, recently shown to be identical to CD49, is somewhat less restricted to NK-lineage cells, 8 and is probably acquired at a later stage. For example, there are NK-1.1 ϩ DX5 Ϫ cells in bone marrow, whereas most NK-1.1 ϩ spleen cells are DX5 ϩ . 9 It is interesting that fetal and neonatal NK cells express high levels of CD94/NKG2A receptors, but not Ly49. The density of CD94/NKG2A gradually declines when Ly49 family receptors are acquired. 10 Although interleukin 2 (IL-2) can be used to drive formation of NK cells in vitro, IL-2-deficient mice and IL-2 receptor ␣ chain (IL-2R␣)-deficient mice have NK cells. 11,12 In contrast, the IL-2R␤, the common ␥ chain (␥c) of the IL-2/IL-7 receptor and the tyrosine kinase JAK3 are all required for generation of NK cells. [13][14][15] First cloned from a human bone marrow stromal cell line, IL-15 uses a receptor composed of an IL-15-specific ␣ chain, the IL-2R␤, and the ␥c. for this cytokine were recently determined to be committed NK-cell progenitors. 9 Similar CD122 ϩ NK precursors can also be derived from multipotent Lin Ϫ Sca-2 ϩ c-kit ϩ progenitors in vitro. 23 Kondo and colleagues ...

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Age and stage dependency of estrogen receptor expression by lymphocyte precursors

Cited by 148 publications

References 52 publications

Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients

Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients

Early Fetal Liver Readily Repopulates B Lymphopoiesis in Adult Bone Marrow

Relationships between early B- and NK-lineage lymphocyte precursors in bone marrow

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