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Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging

Author

Listed:
  • S-C. A. Yeh

    (Harvard Medical School)

  • J. Hou

    (Harvard Medical School)

  • J. W. Wu

    (Harvard Medical School)

  • S. Yu

    (New Jersey Institute of Technology)

  • Y. Zhang

    (New Jersey Institute of Technology)

  • K. D. Belfield

    (New Jersey Institute of Technology)

  • F. D. Camargo

    (Boston Children’s Hospital
    Harvard University)

  • C. P. Lin

    (Harvard Medical School
    Harvard University)

Abstract

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca2+]e), but the local [Ca2+]e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca2+]e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca2+]e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca2+]e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca2+]e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca2+]e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.

Suggested Citation

  • S-C. A. Yeh & J. Hou & J. W. Wu & S. Yu & Y. Zhang & K. D. Belfield & F. D. Camargo & C. P. Lin, 2022. "Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-27973-x
    DOI: 10.1038/s41467-022-27973-x
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    References listed on IDEAS

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    1. Gregor B. Adams & Karissa T. Chabner & Ian R. Alley & Douglas P. Olson & Zbigniew M. Szczepiorkowski & Mark C. Poznansky & Claudine H. Kos & Martin R. Pollak & Edward M. Brown & David T. Scadden, 2006. "Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor," Nature, Nature, vol. 439(7076), pages 599-603, February.
    2. Constantina Christodoulou & Joel A. Spencer & Shu-Chi A. Yeh & Raphaël Turcotte & Konstantinos D. Kokkaliaris & Riccardo Panero & Azucena Ramos & Guoji Guo & Negar Seyedhassantehrani & Tatiana V. Esip, 2020. "Live-animal imaging of native haematopoietic stem and progenitor cells," Nature, Nature, vol. 578(7794), pages 278-283, February.
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