Publication Date:
2014-03-05
Description:
Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells. Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types. However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis, expression of hypoxia inducible factor-1alpha (Hif-1alpha) and related genes, and staining with surrogate hypoxic markers (for example, pimonidazole). Here we perform direct in vivo measurements of local oxygen tension (pO2) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute pO2 of the bone marrow to be quite low (〈32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local pO2, with the lowest pO2 ( approximately 9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal regions. The endosteal region, by contrast, is less hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These pO2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984353/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spencer, Joel A -- Ferraro, Francesca -- Roussakis, Emmanuel -- Klein, Alyssa -- Wu, Juwell -- Runnels, Judith M -- Zaher, Walid -- Mortensen, Luke J -- Alt, Clemens -- Turcotte, Raphael -- Yusuf, Rushdia -- Cote, Daniel -- Vinogradov, Sergei A -- Scadden, David T -- Lin, Charles P -- EB017274/EB/NIBIB NIH HHS/ -- HL096372/HL/NHLBI NIH HHS/ -- HL097748/HL/NHLBI NIH HHS/ -- HL097794/HL/NHLBI NIH HHS/ -- R01 EB014703/EB/NIBIB NIH HHS/ -- R01 EB017274/EB/NIBIB NIH HHS/ -- R01 HL097748/HL/NHLBI NIH HHS/ -- R01 HL097794/HL/NHLBI NIH HHS/ -- R03 HL096372/HL/NHLBI NIH HHS/ -- U01 HL100402/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Apr 10;508(7495):269-73. doi: 10.1038/nature13034. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [3] Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA. ; 1] Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [3] Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia. ; 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [3] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA. ; Departement de Physique, Genie Physique et Optique and Centre de Recherche de l'Institut Universitaire en Sante Mentale de Quebec, Universite Laval, Quebec City, Quebec G1J 2G3, Canada. ; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [2] Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA [3] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590072" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anoxia/diagnosis/metabolism
;
Arteries/metabolism
;
Bone Marrow/blood supply/drug effects/*metabolism/radiation effects
;
Busulfan/pharmacology
;
Cell Hypoxia
;
Hematopoietic Stem Cells/cytology/metabolism
;
Luminescent Measurements
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Microscopy
;
Nestin/metabolism
;
Oxygen/*analysis/metabolism
;
Photons
;
Stem Cell Niche/drug effects/radiation effects
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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