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Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells
Pharmaceutical Science and Research
  • Huilin Shi
  • Christopher A. Drummond
  • Xiaoming Fan
  • Steven T. Haller
  • Jiang Liu, Marshall University
  • Deepak Malhotra
  • Jiang Tian
Document Type
Publication Date
Cardiac progenitor cells including c-kit(+) cells and cardiosphere-derived cells (CDCs) play important roles in cardiac repair and regeneration. CDCs were reported to contain only small subpopulations of c-kit(+) cells and recent publications suggested that depletion of the c-kit(+) subpopulation of cells has no effect on regenerative properties of CDCs. However, our current study showed that the vast majority of CDCs from murine heart actually express c-kit, albeit, in an intracellular and non-glycosylated form. Immunostaining and flow cytometry showed that the fluorescent signal indicative of c-kit immunostaining significantly increased when cell membranes were permeabilized. Western blots further demonstrated that glycosylation of c-kit was increased during endothelial differentiation in a time dependent manner. Glycosylation inhibition by 1-deoxymannojirimycin hydrochloride (1-DMM) blocked c-kit glycosylation and reduced expression of endothelial cell markers such as Flk-1 and CD31 during differentiation. Pretreatment of these cells with a c-kit kinase inhibitor (imatinib mesylate) also attenuated Flk-1 and CD31 expression. These results suggest that c-kit glycosylation and its kinase activity are likely needed for these cells to differentiate into an endothelial lineage. In vivo, we found that intracellular c-kit expressing cells are located in the wall of cardiac blood vessels in mice subjected to myocardial infarction. In summary, our work demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage.

The copy of record is available from the publisher at Copyright © 2016 The Authors. Published b yElsevier B.V. This is an open access article under the CCBY-NC-ND license (

Citation Information
Shi H, Drummond CA, Fan X, et al. Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells. Stem Cell Research. 2016;16(3):795-806. doi:10.1016/j.scr.2016.04.017.