Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and Y chromosome loss following bone marrow transplantation and secondary inflammation

FASEB J. 2007 Aug;21(10):2592-601. doi: 10.1096/fj.06-7861com. Epub 2007 Apr 20.


Cell fusion is one mechanism by which bone marrow-derived cells (BMDCs) take on the gene expression pattern of nonhematopoietic cells. This process occurs in a number of organs with postengraftment injury but has never been found in the lung. We performed bone marrow (BM) transplant in a murine model of lung inflammation to test whether transplanted BMDCs develop lung-specific gene expression by fusing with diseased pneumocytes. Mice lacking the lung-specific protein surfactant protein C (Sp-C) were lethally irradiated, transplanted with sex mismatched wild-type marrow, and sacrificed 6 months later. Nineteen/38 recipients exhibited Sp-C mRNA (RT-PCR) and/or protein (mean 0.95+/-1.18 Sp-C+ cells per 1000 type II pneumocytes by confocal microscopy). In male recipients of female BM, 65% of Sp-C + cells contained the Y chromosome, indicating their origin from fusion. Only 28% of Sp-C+ cells in female recipients of male BMDCs contained the Y chromosome, suggesting that 72% of Sp-C-expressing cells lost the Y chromosome. In the setting of post-transplant inflammation, pneumocyte-specific reprogramming of transplanted BMDCs predominantly derives from heterokaryon formation. This process does not reverse inflammation caused by Sp-C deficiency; nevertheless, further investigation may identify phenotypes benefiting from such an approach.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / pathology
  • Bone Marrow Transplantation / physiology*
  • Chromosome Deletion*
  • Female
  • Inflammation / genetics*
  • Inflammation / physiopathology
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Knockout
  • Peptides / deficiency*
  • Postoperative Complications / physiopathology
  • Pulmonary Surfactant-Associated Protein C
  • Transplantation Chimera
  • Transplantation Conditioning
  • Whole-Body Irradiation
  • Y Chromosome*


  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Pulmonary Surfactant-Associated Protein C
  • Sftpc protein, mouse