ArticleBlood advances2021
Using mitochondrial activity to select for potent human hematopoietic stem cells.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Loss of TCA cycle turning promotes stem cell function.bioRxiv : the preprint server for biology · 2026Article
- Hematopoietic Stem Cell Metabolism during Stress and Aging.Advances in geriatric medicine and research · 2026Article
- Image-enabled cell sorting permits prospective isolation of primitive hematopoietic stem cell subsets with distinct functional potential.Experimental hematology · 2026Article
- Mitochondria: the key hub for hematopoietic stem cell homeostasis maintenance and fate determination.Stem cell research & therapy · 2026Review
- Article
- Stem cell functionbioRxiv : the preprint server for biology · 2026Article
- Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.The Journal of clinical investigation · 2026Article
- Bone marrow neutrophil density regulates myelopoiesis during obesity and weight loss.The Journal of experimental medicine · 2025Article
- Single-cell transcriptomics reveals BMP4-BMPR2 signaling promotes radiation resistance in hematopoietic stem cells following injury.Nature communications · 2025Article
- Restoring mitochondrial function promotes hematopoietic reconstitution from cord blood following cryopreservation-related functional decline.The Journal of clinical investigation · 2025Article
- Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges.International journal of molecular sciences · 2025Review
- Proteomics reveals dynamic metabolic changes in human hematopoietic stem progenitor cells from fetal to adulthood.Stem cell research & therapy · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.Nature reviews. Molecular cell biology · 2023Review
- Innovative Therapeutic Approaches for the Treatment of the Ocular Morbidities in Patients with EEC Syndrome.Cells · 2023Review
- Dlk1 maintains adult mice long-term HSCs by activating Notch signaling to restrict mitochondrial metabolism.Experimental hematology & oncology · 2023Article
- Haematopoietic stem cell quiescence exposed using mitochondrial membrane potential.Current opinion in hematology · 2023Review
- Protocol to identify and analyze mouse and human quiescent hematopoietic stem cells using flow cytometry combined with confocal imaging.STAR protocols · 2022Article
- Mitochondrial Deep Dive into Hematopoietic Stem Cell Dormancy: Not Much Glycolysis but Plenty of Sluggish Lysosomes.Experimental hematology · 2022Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
Hematopoietic cell transplantation is a critical curative approach for many blood disorders. However, obtaining grafts with sufficient numbers of hematopoietic stem cells (HSCs) that maintain long-term engraftment remains challenging; this is due partly to metabolic modulations that restrict the potency of HSCs outside of their native environment. To address this, we focused on mitochondria. We found that human HSCs are heterogeneous in their mitochondrial activity as measured by mitochondrial membrane potential (MMP) even within the highly purified CD34+CD38-CD45RA-CD90+CD49f+ HSC population. We further found that the most potent HSCs exhibit the lowest mitochondrial activity in the population. We showed that the frequency of long-term culture initiating cells in MMP-low is significantly greater than in MMP-high CD34+CD38-CD45RA-CD90+ (CD90+) HSCs. Notably, these 2 populations were distinct in their long-term repopulating capacity when transplanted into immunodeficient mice. The level of chimerism 7 months posttransplantation was >50-fold higher in the blood of MMP-low relative to MMP-high CD90+ HSC recipients. Although more than 90% of both HSC subsets were in G0, MMP-low CD90+ HSCs exhibited delayed cell-cycle priming profile relative to MMP-high HSCs. These functional differences were associated with distinct mitochondrial morphology; MMP-low in contrast to MMP-high HSCs contained fragmented mitochondria. Our findings suggest that the lowest MMP level selects for the most potent, likely dormant, stem cells within the highly purified HSC population. These results identify a new approach for isolating highly potent human HSCs for further clinical applications. They also implicate mitochondria in the intrinsic regulation of human HSC quiescence and potency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.