Skip to main content
SpringerLink
Log in

Hypoxia and Visualization of the Stem Cell Niche

  • Protocol
  • First Online:
Stem Cell Niche

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1035))

Abstract

It is widely accepted that mammalian stem cells reside in a specialized cellular and a cellular microenvironment called the niche. The niche contrary to other tissues is characterized by a low partial Oxygen pressure (ppO2). This microenvironment protects stem cells from deleterious effects of O2 on proteins and DNA, through the production of reactive oxygen species (ROS). In addition there is now solid evidence that this physiological hypoxia helps stem cells maintaining their major characteristics: multipotency and ability to differentiate and migrate from the niche to specialized tissues in order to fulfill the needs of the organism. Immuno Histological techniques can stain stem cells in situ by specific Abs (such as against CD34 and CD45 for Hematopoietic Stem Cells HSC). However, a universal marker of hypoxia is Hypoxia-Inducible Factor-1, HIF-1, which is stabilized by low ppO2 and acts as a transcription factor to regulate a vast array of genes downstream. HIF-1, together with pimonidazole, a chemical compound interacting with proteins that are reduced in a hypoxic environment, are bona fide markers of the stem cell niche.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Scadden DT (2006) The stem cell niche as an identity of action. Nature 441:1075

    Article  PubMed  CAS  Google Scholar 

  2. Brahimi-Horn MC, Pouyssegur J (2007) Oxygen, a source of life and stress. FEBS Lett 581:3582–3591

    Article  PubMed  CAS  Google Scholar 

  3. Eliasson P, Johnsson JI (2010) The hematopoietic stem cell niche: low in oxygen but a nice place to be. J Cell Physiol 222:17–22

    Article  PubMed  CAS  Google Scholar 

  4. Simon MC, Keith B (2008) The role of oxygen availability in embryonic development and stem cell function. Nat Rev Mol Cell Biol 9:285–296

    Article  PubMed  CAS  Google Scholar 

  5. Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6:93–106

    Article  PubMed  CAS  Google Scholar 

  6. Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116:1195–1201

    Article  PubMed  CAS  Google Scholar 

  7. van Tavazoie M, der Velken L, Silva-Vargas V et al (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288

    Article  PubMed  CAS  Google Scholar 

  8. Li Z, Bao S, Wu Q et al (2009) Hypoxia-inducible factors regulate tumorogenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  PubMed  CAS  Google Scholar 

  9. Harrison JS, Rameshvar P, Chang V et al (2002) Oxygen saturation in the bone marrow of healthy volunteers. Blood 99:394

    Article  PubMed  CAS  Google Scholar 

  10. Matsumoto A, Matsumoto S, Sowers AL et al (2005) Absolute oxygen tension (p(O(2)) in murine fatty and muscle tissue as determined by EPR. Magn Reson Med 54:1530–1535

    Article  PubMed  Google Scholar 

  11. Mendez Ferrer S, Michurina TV, Ferraro F et al (2010) Mesenchymal and hematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834

    Article  PubMed  CAS  Google Scholar 

  12. Basciano L, Nemos C, Foliguet B et al (2011) Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status. BMC Biol 12:12–24

    Article  CAS  Google Scholar 

  13. Pistoia V, Raffaghello L (2010) Potential of mesenchymal stem cells for the treatment of autoimmune disorders. Expert Rev Clin Immunol 6:211–218

    Article  PubMed  CAS  Google Scholar 

  14. Rodesch F, Simon P, Jauniaux E (1992) Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 80:283–285

    PubMed  CAS  Google Scholar 

  15. Ito K, Hirao K, Arai K et al (2006) Reactive oxygen species act through p38MAPK to limit the lifespan of hematopoietic stem cells. Nature Med 12:446–451

    Article  PubMed  CAS  Google Scholar 

  16. Estrada JC, Albo C, Benguria A et al (2012) Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetix stability by activating glycolysis. Cell Death Differ 19:743–755

    Article  PubMed  CAS  Google Scholar 

  17. Thotova ZR, Kollipara BJ, Huntly BH et al (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128:325–339

    Article  Google Scholar 

  18. Miyamoto K, Araki KY, Naka K et al (2007) Foxo3a is essential for the maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1:101–112

    Article  PubMed  CAS  Google Scholar 

  19. Son BR, Marquez-Curtis LA, Kurcia M et al (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254–1264

    Article  PubMed  CAS  Google Scholar 

  20. Urao N, Inomata H, Razvi M et al (2008) Role of nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularisation induced by hinlimb ischemia. Circ Res 103:212–220

    Article  PubMed  CAS  Google Scholar 

  21. Piccoli C, d’Aprile A, Ripoli M et al (2007) Bone marrow-derived hematopoietic stem/progenitor cells express multiple isoforms of NADPH oxidase and promote constitutively reactive oxygen species. Biochem Biophys Res Commun 353:965–972

    Article  PubMed  CAS  Google Scholar 

  22. Urao N, McKinney RD, Fukai T et al (2012) NADPH oxidase 2 regulates bone marrow microenvironment following hinlimb ischemia: role in reparative mobilization of progenitor cells. Stem Cells 30:923–934

    Article  PubMed  CAS  Google Scholar 

  23. Vassilopoulos G, Wang PR, Russel DW (2003) Trans-planted bone marrow regenerate liver by cell fusion. Nature 422:901–904

    Article  PubMed  CAS  Google Scholar 

  24. Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ (2007) Short term exposure of multipotent stromal cells to low owygen increases their expression of CX3CR1 and CXCR7 and their engraftment in vivo. PLoS One 2:e416

    Article  PubMed  Google Scholar 

  25. Weidemann A, Johnson RS (2008) Biology of HIF-1 alpha. Cell Death Differ 15:621–627

    Article  PubMed  CAS  Google Scholar 

  26. Wang Y, Wan C, Deng L et al (2007) The hypoxia-inducible factor 1 alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117:1616–1626

    Article  PubMed  CAS  Google Scholar 

  27. Kim JW, Tshernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177–185

    Article  PubMed  Google Scholar 

  28. Gustafsson MV, Zheng X, Pereira T et al (2005) Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell 9:617–628

    Article  PubMed  CAS  Google Scholar 

  29. Lendahl U, Zimmertman LB, McKay MD (1990) CNS stem cells express a new class of intermediate filament proteins. Cell 60:585–595

    Article  PubMed  CAS  Google Scholar 

  30. Levesque JP, Winkler IG, Hendy J et al (2007) Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxia-inducible transcription factor-1 alpha and vascular endothelial factor A in bone marrow. Stem Cells 25:1954–1965

    Article  PubMed  CAS  Google Scholar 

  31. Raleigh JA, Calkin-Adams DP, Rinker LA et al (1998) Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res 58:3765–3768

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology, Nancy Medical School, Université de Lorraine, Nancy, France

    Ali Dalloul

Authors
  1. Ali Dalloul
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Regenerative Medicine Program, Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research, Ottawa, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Dalloul, A. (2013). Hypoxia and Visualization of the Stem Cell Niche. In: Turksen, K. (eds) Stem Cell Niche. Methods in Molecular Biology, vol 1035. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-508-8_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-508-8_17

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-507-1

  • Online ISBN: 978-1-62703-508-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation