bims-mireme Biomed News
on Mitochondria in regenerative medicine
Issue of 2021‒03‒07
nine papers selected by
Brian Spurlock
University of Alabama at Birmingham
  1. Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate.
  2. The Dynamics of Metabolic Characterization in iPSC-Derived Kidney Organoid Differentiation via a Comparative Omics Approach.
  3. Challenges in Studying Stem Cell Metabolism.
  4. CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion.
  5. Lysosomal Regulation of Metabolism in Quiescent Hematopoietic Stem Cells: More than Just Autophagy.
  6. Recent advances in organoid development and applications in disease modeling.
  7. Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming.
  8. Mitochondria are mixed during cell division.
  9. "Empowering" Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?
  1. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00061-8. [Epub ahead of print]28(3): 394-408
    Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate.
    Ram Prosad Chakrabarty, Navdeep S Chandel.
      Recent evidence supports the notion that mitochondrial metabolism is necessary for the determination of stem cell fate. Historically, mitochondrial metabolism is linked to the production of ATP and tricarboxylic acid (TCA) cycle metabolites to support stem cell survival and growth, respectively. However, it is now clear that beyond these canonical roles, mitochondria as signaling organelles dictate stem cell fate and function. In this review, we focus on key conceptual ideas on how mitochondria control mammalian stem cell fate and function through reactive oxygen species (ROS) generation, TCA cycle metabolite production, NAD+/NADH ratio regulation, pyruvate metabolism, and mitochondrial dynamics.
    Keywords:  L-2-HG; ROS; TCA cycle; acetyl-CoA; epigenetics; mitochondrial dynamics; pyruvate
    DOI:  https://doi.org/10.1016/j.stem.2021.02.011
  2. Front Genet. 2021 ;12 632810
    The Dynamics of Metabolic Characterization in iPSC-Derived Kidney Organoid Differentiation via a Comparative Omics Approach.
    Qizheng Wang, Yucui Xiong, Sheng Zhang, Yufei Sui, Cunlai Yu, Peng Liu, Heying Li, Wenjing Guo, Yubo Gao, Aneta Przepiorski, Alan J Davidson, Meijin Guo, Xiao Zhang.
      The use of differentiating human induced pluripotent stem cells (hiPSCs) in mini-tissue organoids provides an invaluable resource for regenerative medicine applications, particularly in the field of disease modeling. However, most studies using a kidney organoid model, focused solely on the transcriptomics and did not explore mechanisms of regulating kidney organoids related to metabolic effects and maturational phenotype. Here, we applied metabolomics coupled with transcriptomics to investigate the metabolic dynamics and function during kidney organoid differentiation. Not only did we validate the dominant metabolic alteration from glycolysis to oxidative phosphorylation in the iPSC differentiation process but we also showed that glycine, serine, and threonine metabolism had a regulatory role during kidney organoid formation and lineage maturation. Notably, serine had a role in regulating S-adenosylmethionine (SAM) to facilitate kidney organoid formation by altering DNA methylation. Our data revealed that analysis of metabolic characterization broadens our ability to understand phenotype regulation. The utilization of this comparative omics approach, in studying kidney organoid formation, can aid in deciphering unique knowledge about the biological and physiological processes involved in organoid-based disease modeling or drug screening.
    Keywords:  induced pluripotent stem cells; kidney organoids; metabolomics; serine metabolism; transcriptomics
    DOI:  https://doi.org/10.3389/fgene.2021.632810
  3. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00066-7. [Epub ahead of print]28(3): 409-423
    Challenges in Studying Stem Cell Metabolism.
    Cesar A Perez-Ramirez, Heather R Christofk.
      The expanding field of stem cell metabolism has been supported by technical advances in metabolite profiling and novel functional analyses. While use of these methodologies has been fruitful, many challenges are posed by the intricacies of culturing stem cells in vitro, along with the distinctive scarcity of adult tissue stem cells and the complexities of their niches in vivo. This review provides an examination of the methodologies used to characterize stem cell metabolism, highlighting their utility while placing a sharper focus on their limitations and hurdles the field needs to overcome for the optimal study of stem cell metabolic networks.
    DOI:  https://doi.org/10.1016/j.stem.2021.02.016
  4. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(20)30581-6. [Epub ahead of print]28(3): 584
    CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion.
    Gianluca L Russo, Giovanna Sonsalla, Poornemaa Natarajan, Christopher T Breunig, Giorgia Bulli, Juliane Merl-Pham, Sabine Schmitt, Jessica Giehrl-Schwab, Florian Giesert, Martin Jastroch, Hans Zischka, Wolfgang Wurst, Stefan H Stricker, Stefanie M Hauck, Giacomo Masserdotti, Magdalena Götz.
      
    DOI:  https://doi.org/10.1016/j.stem.2020.11.017
  5. Cell Stem Cell. 2021 Mar 04. pii: S1934-5909(21)00067-9. [Epub ahead of print]28(3): 374-377
    Lysosomal Regulation of Metabolism in Quiescent Hematopoietic Stem Cells: More than Just Autophagy.
    Saghi Ghaffari.
      The depth of quiescence in hematopoietic stem cells (HSCs) dictates their potency and is sensitive to metabolic perturbations. Recent evidence suggests that lysosomal functions distinct from autophagic processes are pivotal in regulating quiescence versus activation by potential control of the access to a nutrient reservoir required for HSC activation.
    DOI:  https://doi.org/10.1016/j.stem.2021.02.017
  6. Biochim Biophys Acta Rev Cancer. 2021 Feb 25. pii: S0304-419X(21)00026-3. [Epub ahead of print] 188527
    Recent advances in organoid development and applications in disease modeling.
    Sanchita Rauth, Saswati Karmakar, Surinder K Batra, Moorthy P Ponnusamy.
      An improved understanding of stem cell niches, organogenesis, and disease models has paved the way for developing a three-dimensional (3D) organoid culture system. Organoid cultures can be derived from primary tissues (single cells or tissue subunits), induced pluripotent stem cells (iPSCs), or embryonic stem cells (ESCs). As a significant technological breakthrough, 3D organoid models offer a promising approach for understanding the complexities of human diseases ranging from the mechanistic investigation of disease pathogenesis to therapy. Here, we discuss the recent applications, advantages, and limitations of organoids as in vitro models for studying metabolomics, drug development, infectious diseases, and the gut microbiome. We further discuss the use of organoids in cancer modeling using high throughput sequencing approaches.
    Keywords:  Disease modeling; Gut MIcrobiota; Metabolism; Organoids; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.bbcan.2021.188527
  7. Cell Metab. 2021 Mar 02. pii: S1550-4131(21)00059-0. [Epub ahead of print]33(3): 688-690
    Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming.
    Jennyfer Levoux, Alexandre Prola, Peggy Lafuste, Marianne Gervais, Nathalie Chevallier, Zeynab Koumaiha, Kaouthar Kefi, Laura Braud, Alain Schmitt, Azzedine Yacia, Aurélie Schirmann, Barbara Hersant, Mounia Sid-Ahmed, Sabrina Ben Larbi, Katerina Komrskova, Jakub Rohlena, Frederic Relaix, Jiri Neuzil, Anne-Marie Rodriguez.
      
    DOI:  https://doi.org/10.1016/j.cmet.2021.02.003
  8. Nature. 2021 Mar 03.
    Mitochondria are mixed during cell division.
    Till Klecker, Benedikt Westermann.
      
    Keywords:  Cell biology; Imaging
    DOI:  https://doi.org/10.1038/d41586-021-00511-3
  9. Int J Mol Sci. 2021 Feb 12. pii: 1824. [Epub ahead of print]22(4):
    "Empowering" Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?
    Matthias Mietsch, Rabea Hinkel.
      With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the "stem- less" approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.
    Keywords:  aging; cardiovascular; heart; mitochondria; senescence; stem cell; transplantation
    DOI:  https://doi.org/10.3390/ijms22041824
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