Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model.

IF 2.5 4区 医学 Q2 HEMATOLOGY
Samantha M Holmes, Christopher J Wells, Christine Hall, Amy J M McNaughton, Michael J Rauh, Sheela A Abraham
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引用次数: 0

Abstract

The precancerous expansion of hematopoietic cells, termed clonal hematopoiesis (CH), has been correlated to disease development and all-cause mortality. Despite multiple observations that hematopoietic stem cell and progenitors (HSPCs) are significantly affected by both sex and age, there remain few studies quantifying male and female HSPC populations in wild-type and transgenic Tet2 models over time. Here, we determine that male mice (with a hematopoietic deficiency of Tet2 and control) have more Lin-Sca-1+c-kit+ (LSK) cells, that include multipotent progenitor cells (MPPs; LSK CD48-CD150-) and long-term hematopoietic stem cells (LT-HSC; LSK CD48-CD150+) compared with females. LT-HSC, MPP, and progenitor populations were observed to possess equal male/female ratios in mice at 6 weeks of age; however, the LSK compartment was found most susceptible to sex-based effects in transgenic mice between 6 weeks and 4 months. In contrast, all differentiated progenitor populations analyzed in mice were observed to be unaffected by sex between 6 weeks to 4 months. This study provides a comprehensive analysis of bone-sourced HSPCs in Tet2-deficient mouse models and reveals important sex and age considerations that must be taken into account when choosing mice for transgenic studies in C57BL/6 mice.

被称为克隆造血(CH)的造血细胞癌前扩增与疾病发展和全因死亡率有关。尽管多次观察到造血干细胞和祖细胞(HSPCs)受性别和年龄的显著影响,但很少有研究对野生型和转基因 Tet2 模型中的雌雄 HSPC 群体随着时间的推移进行量化。在这里,我们确定与雌性小鼠相比,雄性小鼠(Tet2造血缺陷和对照组)有更多的Lin-Sca-1+c-kit+(LSK)细胞,其中包括多能祖细胞(MPP;LSK CD48-CD150-)和长期造血干细胞(LT-HSC;LSK CD48-CD150+)。据观察,6周龄小鼠的LT-造血干细胞、MPP和祖细胞群具有相同的雄性/雌性比例;然而,在6周至4个月的转基因小鼠中,LSK区系最容易受到性别影响。与此相反,在 6 周至 4 个月期间,对小鼠中所有分化祖细胞群的分析均发现它们不受性别影响。这项研究对Tet2缺陷小鼠模型中的骨源HSPCs进行了全面分析,并揭示了在选择小鼠进行C57BL/6小鼠转基因研究时必须考虑的重要性别和年龄因素。
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来源期刊
Experimental hematology
Experimental hematology 医学-血液学
CiteScore
5.30
自引率
0.00%
发文量
84
审稿时长
58 days
期刊介绍: Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.
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