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Autophagy and Stem Cells

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Autophagy in Health and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Autophagy, as a highly conserved cellular process, can achieve the degradation and recycling of intracellular substances, and is crucial for maintaining cellular homeostasis and remodeling of normal development. Dysfunctions in autophagy would cause a variety of illnesses including cancer, inflammatory bowel disease and neurodegenerative diseases. The unique self-renewal ability and differentiation ability of stem cells can improve these diseases. Therefore, exploring the mechanism of autophagy in maintaining stem cell homeostasis is crucial. Here we review the mechanisms and regulation of autophagy in embryonic stem cells, hematopoietic stem cells, mesenchymal stem cells, neural stem cells, and cancer stem cells. It helps us understand the relationship between autophagy and stem cells. Although there are many unanswered questions, the study of autophagy and stem cell biology can help us to progress in life sciences.

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Abbreviations

ASCs:

Adult stem cells

ATG:

Autophagy-related

BM-MSCs:

Bone marrow MSCs

CMA:

Chaperone-mediated autophagy

ESCs:

Embryonic stem cells

HSCs:

Hematopoietic stem cells

HSPCs:

HSCs and progenitor cells

iPS:

Induced pluripotent stem

LAMP2:

Lysosomal-associated membrane protein 2

MSCs:

Mesenchymal stem cells

NSCs:

Neural stem cells

ROS:

Reactive oxygen stress

SD-MSCs:

Serum-deprived MSCs

SGZ:

Subgranular zone

SVZ:

Subventricular zone

References

  1. Klionsky DJ. Autophagy revisited: a conversation with Christian de Duve. Autophagy. 2008;4(6):740–3.

    Article  PubMed  Google Scholar 

  2. Kim KH, Lee MS. Autophagy--a key player in cellular and body metabolism. Nat Rev Endocrinol. 2014;10(6):322.

    Article  CAS  PubMed  Google Scholar 

  3. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Investig. 2005;115(10):2679–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Komatsu M, et al. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol. 2005;169(3):425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24(1):92–104.

    Article  CAS  PubMed  Google Scholar 

  6. Galluzzi L, et al. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16(7):487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang J, et al. Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy. Cell Mol Life Sci. 2018;75:1803.

    Article  CAS  PubMed  Google Scholar 

  8. Mizushima N, Yoshimori T, Ohsumi Y. The role of atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27(1):107.

    Article  CAS  PubMed  Google Scholar 

  9. Ke B, et al. Targeting programmed cell death using small-molecule compounds to improve potential cancer therapy. Med Res Rev. 2016;36(6):983–1035.

    Article  PubMed  Google Scholar 

  10. Hosokawa N, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009;20(7):1981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang HJ, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20(7):1992.

    Article  Google Scholar 

  12. Chang YY, Neufeld TP. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell. 2009;20(7):2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Itakura E, et al. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19(12):5360–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Di BS, et al. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol. 2011;191(1):155–68.

    Google Scholar 

  15. Axe EL, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182(4):685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Polson HE, et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6(4):506.

    Article  CAS  PubMed  Google Scholar 

  17. Mizushima N, et al. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem. 1998;273(51):33889–92.

    Article  CAS  PubMed  Google Scholar 

  18. Mizushima N, et al. A protein conjugation system essential for autophagy. Nature. 1998;395(6700):395–8.

    Article  CAS  PubMed  Google Scholar 

  19. Kuma A, et al. Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem. 2002;277(21):18619.

    Article  CAS  PubMed  Google Scholar 

  20. Kabeya Y, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19(21):5720–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tanida I, et al. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates. J Biol Chem. 2004;279(35):36268–76.

    Article  CAS  PubMed  Google Scholar 

  22. Ichimura Y, et al. A ubiquitin-like system mediates protein lipidation. Nature. 2000;408(6811):488.

    Article  CAS  PubMed  Google Scholar 

  23. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000;290(5497):1717–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yu L, et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010;465(7300):942–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shen R, et al. The function and regulation of BMP6 in various kinds of stem cells. Curr Pharm Des. 2015;21(25):3634–43.

    Article  CAS  PubMed  Google Scholar 

  26. He S, Nakada D, Morrison SJ. Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol. 2009;25(25):377.

    CAS  PubMed  Google Scholar 

  27. Bongso A, Lee EH. Stem cells: their definition, classification and sources. Stem Cells. London: World Scientific Publishing Co. Pte. Ltd.; 1935. p. 1–13.

    Google Scholar 

  28. Dave M, et al. Mesenchymal stem cell therapy for inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2015;21(11):2696.

    Article  PubMed  Google Scholar 

  29. Hsieh MM, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361(24):2309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Laird DJ, Andrian UHV, Wagers AJ. Stem cell trafficking in tissue development, growth, and disease. Cell. 2008;132(4):612.

    Article  CAS  PubMed  Google Scholar 

  31. Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci. 2000;113(Pt 1):5.

    CAS  PubMed  Google Scholar 

  32. Pera MF, Dottori M. Stem cells and their developmental potential. Singapore: World Scientific Publishing; 2015. p. 55–70.

    Google Scholar 

  33. Guan JL, et al. Autophagy in stem cells. Autophagy. 2013;9(6):830–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    Article  CAS  PubMed  Google Scholar 

  35. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981;78(12):7634–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bradley A, et al. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature. 1984;309(5965):255–6.

    Article  CAS  PubMed  Google Scholar 

  37. Ross EA, Anderson N, Micklem HS. Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging. J Exp Med. 1982;155(2):432–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132(4):631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kumaravelu P, et al. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development. 2002;129(21):4891.

    CAS  PubMed  Google Scholar 

  40. Rhodes KE, et al. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell. 2008;2(3):252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pittenger MF, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.

    Article  CAS  PubMed  Google Scholar 

  42. Majumdar MK, et al. Phenotypic and functional comparison of cultures of marrow‐derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol. 1998;176(1):57–66.

    Article  CAS  PubMed  Google Scholar 

  43. Caplan AI. The mesengenic process. Clin Plast Surg. 1994;21(3):429.

    CAS  PubMed  Google Scholar 

  44. Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol. 2011;12(2):126–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li W, et al. Autophagy is required for human umbilical cord mesenchymal stem cells to improve spatial working memory in APP/PS1 transgenic mouse model. Stem Cell Res Ther. 2018;9(1):9.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Maitra B, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant. 2004;33(6):597–604.

    Article  CAS  PubMed  Google Scholar 

  47. Groszer M, et al. PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry. Proc Natl Acad Sci U S A. 2006;103(1):111–6.

    Article  CAS  PubMed  Google Scholar 

  48. Jackson EL, et al. PDGFRα-Positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron. 2006;51(2):187–99.

    Article  CAS  PubMed  Google Scholar 

  49. Hermanson O, Jepsen K, Rosenfeld MG. N-CoR controls differentiation of neural stem cells into astrocytes. Nature. 2002;419(6910):934–9.

    Article  CAS  PubMed  Google Scholar 

  50. Aguirre A, Rubio ME, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature. 2010;467(7313):323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433.

    Article  CAS  PubMed  Google Scholar 

  52. Phadwal K, Watson AS, Simon AK. Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. Cell Mol Life Sci. 2013;70(1):89–103.

    Article  CAS  PubMed  Google Scholar 

  53. Vessoni AT, Muotri AR, Okamoto OK. Autophagy in stem cell maintenance and differentiation. Stem Cells Dev. 2012;21(4):513–20.

    Article  CAS  PubMed  Google Scholar 

  54. Tooze J, Davies HG. Cytolysomes in amphibian erythrocytes. J Cell Biol. 1965;24(1):146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kent G, et al. Autophagic vacuoles in human red cells. Am J Pathol. 1966;48(48):831–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kundu M, et al. Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood. 2008;112(4):1493–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Thomson JA, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145.

    Article  CAS  PubMed  Google Scholar 

  58. Chen Y, Klionsky DJ. The regulation of autophagy – unanswered questions. J Cell Sci. 2011;124(Pt 2):161–70.

    Article  CAS  PubMed  Google Scholar 

  59. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009;43(1):67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mizushima N, et al. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol. 2001;152(4):657–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tsukamoto S, et al. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321(5885):117–20.

    Article  CAS  PubMed  Google Scholar 

  62. Wang S, et al. Transient activation of autophagy via Sox2-mediated suppression of mTOR is an important early step in reprogramming to pluripotency. Cell Stem Cell. 2013;13(5):617.

    Article  CAS  PubMed  Google Scholar 

  63. Mizushima N. Aβ generation in autophagic vacuoles. J Cell Biol. 2005;171(1):15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cho YH, et al. Autophagy regulates homeostasis of pluripotency-associated proteins in hESCs. Stem Cells. 2014;32(2):424–35.

    Article  CAS  PubMed  Google Scholar 

  65. Tra T, et al. Autophagy in human embryonic stem cells. PLoS One. 2011;6(11):e27485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Qu X, et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell. 2007;128(5):931–46.

    Article  CAS  PubMed  Google Scholar 

  67. Saitoh T, et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A. 2009;106(49):20842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sou YS, et al. The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell. 2008;19(11):4762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kuma A, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004;432(7020):1032–6.

    Article  CAS  PubMed  Google Scholar 

  70. Levine B. Autophagy in mammalian development and differentiation. Nat Cell Biol. 2010;12(9):823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Boya P, Codogno P, Rodriguez-Muela N. Autophagy in stem cells: repair, remodelling and metabolic reprogramming. Development. 2018;145(4):pii: dev146506.

    Article  CAS  Google Scholar 

  72. Yue Z, et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A. 2003;100(25):15077–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chen S, et al. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model. Genes Dev. 2016;30(7):856–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kaizuka T, Mizushima N. Atg13 is essential for autophagy and cardiac development in mice. Mol Cell Biol. 2016;36(4):585–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kuo TC, et al. Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity. Nat Cell Biol. 2011;13(10):1214–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Schink KO, et al. Cell differentiation: midbody remnants — junk or fate factors? Curr Biol. 2011;21(23):958–60.

    Article  CAS  Google Scholar 

  77. Isakson P, et al. TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy. Autophagy. 2013;9(12):1955.

    Article  CAS  PubMed  Google Scholar 

  78. Mandell MA, et al. TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. J Cell Sci. 2016;129(19):3562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mortensen M, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011;208(3):455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Warr MR, et al. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature. 2013;494(7437):323–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu F, Guan JL. FIP200, an essential component of mammalian autophagy is indispensible for fetal hematopoiesis. Autophagy. 2011;7(2):229.

    Article  CAS  PubMed  Google Scholar 

  82. Salemi S, et al. Autophagy is required for self-renewal and differentiation of adult human stem cells. Cell Res. 2012;22(2):432.

    Article  CAS  PubMed  Google Scholar 

  83. Liu F, et al. FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood. 2010;116(23):4806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kang Y, et al. Autophagy driven by a master regulator of hematopoiesis. Mol Cell Biol. 2012;32(1):226–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Iwama A, et al. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004;21(6):843.

    Article  CAS  PubMed  Google Scholar 

  86. Park IK, et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature. 2003;423(6937):302.

    Article  CAS  PubMed  Google Scholar 

  87. Yahata T, et al. Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells. Blood. 2011;118(11):2941.

    Article  CAS  PubMed  Google Scholar 

  88. Joshi A, Kundu M. Mitophagy in hematopoietic stem cells: the case for exploration. Autophagy. 2013;9(11):1737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Chong C, et al. TSC–mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med. 2008;205(10):2397.

    Article  Google Scholar 

  90. Chen C, et al. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal. 2009;2(98):ra75.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Mortensen M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Autophagy. 2010;107(3):832–7.

    CAS  Google Scholar 

  92. Yan C, et al. ROS functions as an upstream trigger for autophagy to drive hematopoietic stem cell differentiation. Hematology. 2016;21(10):1.

    Google Scholar 

  93. Cao Y, et al. Autophagy sustains hematopoiesis through targeting notch. Stem Cells Dev. 2015;24(22):2660.

    Article  CAS  PubMed  Google Scholar 

  94. Cao Y, et al. Hierarchal autophagic divergence of hematopoietic system. J Biol Chem. 2015;290(38):23050–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Yuan X, et al. Mitochondrial apoptosis and autophagy in the process of adipose‐derived stromal cell differentiation into astrocytes. Cell Biol Int. 2016;40(2):156–65.

    Article  CAS  PubMed  Google Scholar 

  96. Denis JA, et al. mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1. J Cell Sci. 2013;126(8):1763–72.

    Article  CAS  PubMed  Google Scholar 

  97. Shang YC, et al. Prevention of β-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL. Aging. 2012;4(3):187–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Walls KC, et al. Lysosome dysfunction triggers Atg7-dependent neural apoptosis. J Biol Chem. 2010;285(14):10497–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Jiao Q. et al. [An overview on autophagy in neural stem cells]. Sheng li xue bao : [Acta Physiologica Sinica]. 2016; 68(5): 649.

    Google Scholar 

  100. Zeng M, Zhou JN. Roles of autophagy and mTOR signaling in neuronal differentiation of mouse neuroblastoma cells. Cell Signal. 2008;20(4):659.

    Article  CAS  PubMed  Google Scholar 

  101. Li M, et al. EVA1A/TMEM166 regulates embryonic neurogenesis by autophagy. Stem Cell Rep. 2016;6(3):396–410.

    Article  CAS  Google Scholar 

  102. Vázquez P, et al. Atg5 and Ambra1 differentially modulate neurogenesis in neural stem cells. Autophagy. 2012;8(2):187.

    Article  CAS  PubMed  Google Scholar 

  103. Belle JEL, et al. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell. 2011;8(1):59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Han X, et al. AMPKactivation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellularNAD+elevation. Aging Cell. 2016;15(3):416–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wang C, et al. FIP200 is required for maintenance and differentiation of postnatal neural stem cells. Nat Neurosci. 2013;16(5):532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Zhu L, et al. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy. Biochem Biophys Res Commun. 2015;464(2):526–33.

    Article  CAS  PubMed  Google Scholar 

  107. Chuikov S, et al. Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress. Nat Cell Biol. 2010;12(10):999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Paik J, et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 2009;5(5):540–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Molaei S, et al. Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions. Blood Res. 2015;50(2):80–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Oliver L, et al. Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells. Stem Cells Dev. 2012;21(15):2779.

    Article  CAS  PubMed  Google Scholar 

  111. Li B, et al. Role of autophagy on bone marrow mesenchymal stem‑cell proliferation and differentiation into neurons. Mol Med Rep. 2016;13(2):1413–9.

    Article  CAS  PubMed  Google Scholar 

  112. Wan Y, et al. Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae. Biochem Biophys Res Commun. 2017;488:46.

    Article  CAS  PubMed  Google Scholar 

  113. Karch J, et al. Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. Elife. 2017;6:e30543.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Musumeci G, et al. Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis. Int J Mol Sci. 2015;16(9):20560–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zhang Q, et al. Autophagy activation: a novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase/mammalian target of rapamycin pathway. Stem Cells Dev. 2012;21(8):1321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sanchez CG, et al. Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis. 2011;32(7):964–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17(3):313–9.

    Article  CAS  PubMed  Google Scholar 

  118. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21(3):283–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Visvader J, Lindeman G. cancer stem cells: current status and evolving complexities. Cell Stem Cell. 2012;10(6):717.

    Article  CAS  PubMed  Google Scholar 

  120. Gong C, et al. Beclin 1 and autophagy are required for the tumorigenicity of breast cancer stem-like/progenitor cells. Autophagy. 2012;8(12):1853–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Liang XH, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402(6762):672.

    Article  CAS  PubMed  Google Scholar 

  122. Espina V, et al. Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival. PLoS One. 2010;5(4):e10240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Maycotte P, et al. Autophagy supports breast cancer stem cell maintenance by regulating IL6 secretion. Mol Cancer Res. 2015;13(4):651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Cufã SL, et al. Autophagy positively regulates the CD44+CD24-/low breast cancer stem-like phenotype. Cell Cycle. 2011;10(22):3871–85.

    Article  CAS  Google Scholar 

  125. Galluzzi L, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34(7):856–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Yue W, et al. ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models. Stem Cell Rep. 2015;5(5):776.

    Article  CAS  Google Scholar 

  127. Wu QY, et al. Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer’s disease rat model. Neurosci Lett. 2007;417(3):281–5.

    Article  CAS  PubMed  Google Scholar 

  128. Hargus G, et al. Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development. Acta Neuropathol. 2014;127(2):151.

    Article  CAS  PubMed  Google Scholar 

  129. Dalby KN, et al. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy. 2010;6(3):322–9.

    Article  CAS  PubMed  Google Scholar 

  130. Buchser WJ, et al. Cell-mediated autophagy promotes cancer cell survival. Cancer Res. 2012;72(12):2970–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China

    Kai Li & Zhuo Yang

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  1. Kai Li
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Correspondence to Zhuo Yang .

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    Kursad Turksen

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Li, K., Yang, Z. (2018). Autophagy and Stem Cells. In: Turksen, K. (eds) Autophagy in Health and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98146-8_1

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