Normal Hematopoetic Stem and Progenitor Cells Can Exhibit Metabolic Flexibility Similar to Cancer Cells
Copyright © 2020 Vlaski-Lafarge, Labat, Brandy, Refeyton, Duchez, Rodriguez, Gibson, Brunet de la Grange and Ivanovic..
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+CD38lowCD133+CD90+CD45RA- population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic ("ischemia-like"), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 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 (~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% O2. 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 O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in oncology - 10(2020) vom: 07., Seite 713 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vlaski-Lafarge, Marija [VerfasserIn] |
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| Links: |
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| Themen: |
Bioenergetics |
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| Anmerkungen: |
Date Revised 28.09.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2020.00713 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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+CD38lowCD133+CD90+CD45RA- population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic ("ischemia-like"), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 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 (~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% O2. 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 O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness | ||
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| 650 | 4 | |a cancer stem cells | |
| 650 | 4 | |a hematopoietic stem cells | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a mitochondrial respiration | |
| 700 | 1 | |a Labat, Veronique |e verfasserin |4 aut | |
| 700 | 1 | |a Brandy, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Refeyton, Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Duchez, Pascale |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Gibson, Nyere |e verfasserin |4 aut | |
| 700 | 1 | |a Brunet de la Grange, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Ivanovic, Zoran |e verfasserin |4 aut | |
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