4.6 Article

Normal Hematopoetic Stem and Progenitor Cells Can Exhibit Metabolic Flexibility Similar to Cancer Cells

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FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.00713

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cancer stem cells; hematopoietic stem cells; metabolism; bioenergetics; mitochondrial respiration

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  1. Etablissement Francais du Sang Nouvelle Aquitaine Bordeaux, regional research and development budget

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It is known that cancer stem cells (CSCs) with the largest proliferative capacity survive the anoxic and/or ischemic conditions present inside tumorous tissue. In this study we test whether normal stem cells can survive under the same conditions due to cancer cell-like metabolic adaptations. We cultivated a CD34(+) population with a majority of hematopoietic progenitors, and a CD34(+)CD38(low)CD133(+)CD90(+)CD45RA(-) population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic (ischemia-like), or physiological conditions (3% O-2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O-2 concentration; CD34(+) cells, aldehyde dehydrogenase-expressing primitive cells, and committed progenitors expanded, even in anoxia. Interestingly, under ischemia-like conditions, stem and CD34(+) cell populations are maintained at day-0 level. Cell-cycle analysis further revealed an accumulation of cells in the G0/G1 phase in anoxia or anoxia/aglycemia, with a fraction of cells (similar to 40%) actively cycling (SG2M phases). Also stem cell analysis showed that in these conditions a long-term Scid Repopulating activity was equal to that found with 3% O-2. In addition stem cells with the highest proliferative capacity were maintained in anoxia/aglycemia and in anoxia. The estimated ATP profile, active mitochondrial content, and succinate accumulation are indicative of anaerobic mitochondrial respiration in both HSCs and CD34(+) progenitors under ischemia-like conditions. We demonstrate here that primitive hematopoietic cells show similar metabolic flexibility to CSCs, allowing them to survive a lack of O-2 and O-2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.

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