Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription.
OBJECTIVE
Microvesicles have been shown to mediate intercellular communication. Previously, we have correlated entry of murine lung-derived microvesicles into murine bone marrow cells with expression of pulmonary epithelial cell-specific messenger RNA (mRNA) in these marrow cells. The present studies establish that entry of lung-derived microvesicles into marrow cells is a prerequisite for marrow expression of pulmonary epithelial cell-derived mRNA.


METHODS
Murine bone marrow cells cocultured with rat lung, but separated from them using a cell-impermeable membrane (0.4-microm pore size), were analyzed using species-specific primers (for rat or mouse).


RESULTS
These studies revealed that surfactant B and C mRNA produced by murine marrow cells were of both rat and mouse origin. Similar results were obtained using murine lung cocultured with rat bone marrow cells or when bone marrow cells were analyzed for the presence of species-specific albumin mRNA after coculture with rat or murine liver. These studies show that microvesicles both deliver mRNA to marrow cells and mediate marrow cell transcription of tissue-specific mRNA. The latter likely underlies the longer-term stable change in genetic phenotype that has been observed. We have also observed microRNA in lung-derived microvesicles, and studies with RNase-treated microvesicles indicate that microRNA negatively modulates pulmonary epithelial cell-specific mRNA levels in cocultured marrow cells. In addition, we have also observed tissue-specific expression of brain, heart, and liver mRNA in cocultured marrow cells, suggesting that microvesicle-mediated cellular phenotype change is a universal phenomena.


CONCLUSIONS
These studies suggest that cellular systems are more phenotypically labile than previously considered.
Aliotta
Jason M
JM
Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Providence, RI 02903, USA. jaliotta@lifespan.org
Pereira
Mandy
M
Johnson
Kevin W
KW
de Paz
Nicole
N
Dooner
Mark S
MS
Puente
Napoleon
N
Ayala
Carol
C
Brilliant
Kate
K
Berz
David
D
Lee
David
D
Ramratnam
Bharat
B
McMillan
Paul N
PN
Hixson
Douglas C
DC
Josic
Djuro
D
Quesenberry
Peter J
PJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D003594:Cytoplasmic Granules; D055354:Exosomes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D011510:Proteolipids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic
D017077:Culture Media, Conditioned; D010455:Peptides; D011498:Protein Precursors; D011510:Proteolipids; D012333:RNA, Messenger; C105511:surfactant protein B propeptide; C077063:Sftpc protein, rat