Hematopoietic stem/progenitor cells express functional mitochondrial energy-dependent cystic fibrosis transmembrane conductance regulator

Donatella Piro, Claudia Piccoli, Lorenzo Guerra, Francesca Sassone, Annamaria D'Aprile, Maria Favia, Stefano Castellani, Sante Di Gioia, Silvia Lepore, Maria Luisa Garavaglia, Teresa Trotta, Angela Bruna Maffione, Valeria Casavola, Giuliano Meyer, Nazzareno Capitanio, Massimo Conese

Research output: Contribution to journalArticle

Abstract

Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine. Cystic fibrosis (CF) is one of the diseases whose hope of cure relies on the successful application of cell-based gene therapy. This study was aimed at characterizing murine HSPCs on the basis of their bioenergetic competence and CF transmembrane conductance regulator (CFTR) expression. Positively immunoselected Sca-1 + HSPCs encompassed 2 populations distinguished by their different size, Sca-1 expression and mitochondrial content. The smaller were the cells, the higher was Sca-1 expression and the lower was the intracellular density of functional mitochondria. Reverse transcription-polymerase chain reaction and western blotting revealed that HSPCs expressed CFTR mRNA and protein, which was also functional, as assessed by spectrofluorimetric and patch-clamp techniques. Inhibition of mitochondrial oxidative phosphorylation by oligomycin resulted in a 70% decrease of both the intracelluar adenosine triphosphate content and CFTR-mediated channel activity. Finally, HSPCs with lower Sca-1 expression and higher mitochondrial content displayed higher CFTR levels. Our findings identify 2 subpopulations in HSPCs and unveil a so-far unappreciated relationship between bioenergetic metabolism and CFTR in HSPC biology.

Original languageEnglish
Pages (from-to)634-646
Number of pages13
JournalStem Cells and Development
Volume21
Issue number4
DOIs
Publication statusPublished - Mar 1 2012

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

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    Piro, D., Piccoli, C., Guerra, L., Sassone, F., D'Aprile, A., Favia, M., Castellani, S., Di Gioia, S., Lepore, S., Garavaglia, M. L., Trotta, T., Maffione, A. B., Casavola, V., Meyer, G., Capitanio, N., & Conese, M. (2012). Hematopoietic stem/progenitor cells express functional mitochondrial energy-dependent cystic fibrosis transmembrane conductance regulator. Stem Cells and Development, 21(4), 634-646. https://doi.org/10.1089/scd.2011.0041