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.
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.