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

作者：Shu-Chi Yeh, Jianquan Hou, Jinmin Wu, Shuhui Yu, Yuekang Zhang, Kevin D. Belfield, Fernando D. Camargo, Charles P. Lin · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-27973-x · 被引用次数：48 · 研究领域：Hematopoietic Stem Cell Transplantation、Neonatal Respiratory Health Research、Immune Response and Inflammation

Abstract The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca 2+ ] e ), but the local [Ca 2+ ] e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca 2+ ] e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca 2+ ] e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.