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The downregulated membrane expression of CD18 in CD34+ cells defines a primitive population of human hematopoietic stem cells.

ABSTRACT: BACKGROUND:CD18 is the common beta subunit of ?2 integrins, which are expressed on hematopoietic cells. ?2 integrins are essential for cell adhesion and leukocyte trafficking. METHODS:Here we have analyzed the expression of CD18 in different subsets of human hematopoietic stem and progenitor cells (HSPCs) from cord blood (CB), bone marrow (BM), and mobilized peripheral blood (mPB) samples. CD34+ cells were classified into CD18high and CD18low/neg, and each of these populations was analyzed for the expression of HSPC markers, as well as for their clonogenity, quiescence state, and repopulating ability in immunodeficient mice. RESULTS:A downregulated membrane expression of CD18 was associated with a primitive hematopoietic stem cells (HSC) phenotype, as well as with a higher content of quiescent cells and multipotent colony-forming cells (CFCs). Although no differences in the short-term repopulating potential of CD18low/neg CD34+ and CD18high CD34+ cells were observed, CD18low/neg CD34+ cells were characterized by an enhanced long-term repopulating ability in NSG mice. CONCLUSIONS:Overall, our results indicate that the downregulated membrane expression of CD18 characterizes a primitive population of human hematopoietic repopulating cells.

SUBMITTER: Mesa-Nunez C

PROVIDER: S-EPMC7189462 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The downregulated membrane expression of CD18 in CD34<sup>+</sup> cells defines a primitive population of human hematopoietic stem cells.

Mesa-Núñez Cristina C Leon-Rico Diego D Aldea Montserrat M Damián Carlos C Sanchez-Baltasar Raquel R Sanchez Rebeca R Alberquilla Omaira O Segovia José Carlos JC Bueren Juan Antonio JA Almarza Elena E

Stem cell research & therapy 20200428 1

<h4>Background</h4>CD18 is the common beta subunit of β<sub>2</sub> integrins, which are expressed on hematopoietic cells. β<sub>2</sub> integrins are essential for cell adhesion and leukocyte trafficking.<h4>Methods</h4>Here we have analyzed the expression of CD18 in different subsets of human hematopoietic stem and progenitor cells (HSPCs) from cord blood (CB), bone marrow (BM), and mobilized peripheral blood (mPB) samples. CD34<sup>+</sup> cells were classified into CD18<sup>high</sup> and CD ...[more]

PMID: 32345365

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Project description:Alpha tocopherol acetate (αTOA) is an analogue of alpha tocopherol (αTOC) that exists in the form of an injectable drug. In the context of the metabolic hypothesis of stem cells, we studied the impact of αTOA on the metabolic energetic profile and functional properties of hematopoietic stem and progenitor cells. In ex vivo experiments performed on cord blood CD34+ cells, we found that αTOA effectively attenuates oxidative phosphorylation without affecting the glycolysis rate. This effect concerns complex I and complex II of the mitochondrial respiratory chain and is related to the relatively late increase (3 days) in ROS (Reactive Oxygen Species). The most interesting effect was the inhibition of Hypoxia-Inducible Factor (HIF)-2α (Hexpression, which is a determinant of the most pronounced biological effect-the accumulation of CD34+ cells in the G0 phase of the cell cycle. In parallel, better maintenance of the primitive stem cell activity was revealed by the expansion seen in secondary cultures (higher production of colony forming cells (CFC) and Severe Combined Immunodeficiency-mice (scid)-repopulating cells (SRC)). While the presence of αTOA enhanced the maintenance of Hematopoietic Stem Cells (HSC) and contained their proliferation ex vivo, whether it could play the same role in vivo remained unknown. Creating αTOC deficiency via a vitamin E-free diet in mice, we found an accelerated proliferation of CFC and an expanded compartment of LSK (lineagenegative Sca-1+cKit+) and SLAM (cells expressing Signaling Lymphocytic Activation Molecule family receptors) bone marrow cell populations whose in vivo repopulating capacity was decreased. These in vivo data are in favor of our hypothesis that αTOC may have a physiological role in the maintenance of stem cells. Taking into account that αTOC also exhibits an effect on proliferative capacity, it may also be relevant for the ex vivo manipulation of hematopoietic stem cells. For this purpose, low non-toxic doses of αTOA should be used.

Dataset Information

The downregulated membrane expression of CD18 in CD34+ cells defines a primitive population of human hematopoietic stem cells.

Publications

The downregulated membrane expression of CD18 in CD34<sup>+</sup> cells defines a primitive population of human hematopoietic stem cells.

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