Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0022116 (
ischemia
)
91,303
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 (~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.
...
PMID:Normal Hematopoetic Stem and Progenitor Cells Can Exhibit Metabolic Flexibility Similar to Cancer Cells. 3252 78
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