Challenges in Studying Stem Cell Metabolism

Perez-Ramirez, Cesar A.; Christofk, Heather R.

doi:10.1016/j.stem.2021.02.016

Cited by 23 publications

(23 citation statements)

References 172 publications

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“…To test this, we sought to directly assess the impact of clock disruption on ASC metabolism following muscle tissue injury. A major limitation of stem cell research is the technical difficulty associated with the measurement of metabolites in rare cell populations ( Perez-Ramirez and Christofk 2021 ). To overcome this problem, we adapted a recently developed method by DeVilbiss et al (2021) to profile metabolite content in as little as 10,000 freshly isolated MuSCs.…”

Section: Resultsmentioning

confidence: 99%

“…While metabolic regulation is an important factor in MuSC maintenance and differentiation, there remains a major challenge in stem cell metabolite profiling due to their low abundance ( Perez-Ramirez and Christofk 2021 ). Here, we have performed the first, to our knowledge, metabolomic profiling study of ∼10,000 MuSCs taken directly from mouse muscle tissue both preinjury and postinjury.…”

Section: Discussionmentioning

confidence: 99%

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BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells

et al. 2022

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The process of tissue regeneration occurs in a developmentally timed manner, yet the role of circadian timing is not understood. Here, we identify a role for the adult muscle stem cell (MuSC)-autonomous clock in the control of muscle regeneration following acute ischemic injury. We observed greater muscle repair capacity following injury during the active/wake period as compared with the inactive/rest period in mice, and loss of Bmal1 within MuSCs leads to impaired muscle regeneration. We demonstrate that Bmal1 loss in MuSCs leads to reduced activated MuSC number at day 3 postinjury, indicating a failure to properly expand the myogenic precursor pool. In cultured primary myoblasts, we observed that loss of Bmal1 impairs cell proliferation in hypoxia (a condition that occurs in the first 1–3 d following tissue injury in vivo), as well as subsequent myofiber differentiation. Loss of Bmal1 in both cultured myoblasts and in vivo activated MuSCs leads to reduced glycolysis and premature activation of prodifferentiation gene transcription and epigenetic remodeling. Finally, hypoxic cell proliferation and myofiber formation in Bmal1-deficient myoblasts are restored by increasing cytosolic NAD+. Together, we identify the MuSC clock as a pivotal regulator of oxygen-dependent myoblast cell fate and muscle repair through the control of the NAD+-driven response to injury.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells

et al. 2022

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“…Christofk also discussed the need for better methods and tools to study in vivo tissue stem cell metabolism and draw causal relationships between metabolism and cell fate change 100 . She showed one new approach of using antibody‐conjugated magnetic beads for rapid isolation of hair follicle stem cells for metabolomic characterization, eliminating the long times and mechanical stress imposed by cell sorting.…”

Section: Metabolic Disordersmentioning

confidence: 99%

Metabolic decisions in development and disease—a Keystone Symposia report

Cable¹,

Pourquié

Wellen

et al. 2021

Annals of the New York Academy of Sciences

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There is an increasing appreciation for the role of metabolism in cell signaling and cell decision making. Precise metabolic control is essential in development, as evident by the disorders caused by mutations in metabolic enzymes. The metabolic profile of cells is often cell‐type specific, changing as cells differentiate or during tumorigenesis. Recent evidence has shown that changes in metabolism are not merely a consequence of changes in cell state but that metabolites can serve to promote and/or inhibit these changes. Metabolites can link metabolic pathways with cell signaling pathways via several mechanisms, for example, by serving as substrates for protein post‐translational modifications, by affecting enzyme activity via allosteric mechanisms, or by altering epigenetic markers. Unraveling the complex interactions governing metabolism, gene expression, and protein activity that ultimately govern a cell's fate will require new tools and interactions across disciplines. On March 24 and 25, 2021, experts in cell metabolism, developmental biology, and human disease met virtually for the Keystone eSymposium, “Metabolic Decisions in Development and Disease.” The discussions explored how metabolites impact cellular and developmental decisions in a diverse range of model systems used to investigate normal development, developmental disorders, dietary effects, and cancer‐mediated changes in metabolism.

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“…VOCs and other metabolites can be identified using various metabolomics techniques, such as mass spectrometry and nuclear magnetic resonance based methods [32,33]. Various VOCs have already been identified in PSCs [34,35].…”

Section: Introductionmentioning

confidence: 99%

“…Analytical platforms used to measure metabolites are generally invasive, lack sensitivity, and require complicated sample preparation [32]. Selected-ion flow-tube mass spectrometry (SIFT-MS) is an analytical technique that can overcome some of these issues.…”

Section: Introductionmentioning

confidence: 99%

Physiological Oxygen Causes the Release of Volatile Organic Compounds from Human Pluripotent Stem Cells with Possible Roles in Maintaining Self-Renewal and Pluripotency

Barreto¹,

Al-Zubaidi²,

Dale³

et al. 2022

Preprint

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Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

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Challenges in Studying Stem Cell Metabolism

Cited by 23 publications

References 172 publications

BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells

BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells

Metabolic decisions in development and disease—a Keystone Symposia report

Physiological Oxygen Causes the Release of Volatile Organic Compounds from Human Pluripotent Stem Cells with Possible Roles in Maintaining Self-Renewal and Pluripotency

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Challenges in Studying Stem Cell Metabolism

Cited by 23 publications

References 172 publications

BMAL1 drives muscle repair through control of hypoxic NAD+ regeneration in satellite cells

BMAL1 drives muscle repair through control of hypoxic NAD+ regeneration in satellite cells

Metabolic decisions in development and disease—a Keystone Symposia report

Physiological Oxygen Causes the Release of Volatile Organic Compounds from Human Pluripotent Stem Cells with Possible Roles in Maintaining Self-Renewal and Pluripotency

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BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells

BMAL1 drives muscle repair through control of hypoxic NAD⁺ regeneration in satellite cells