PMID- 24009878
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130906
LR  - 20220410
IS  - 2001-3078 (Print)
IS  - 2001-3078 (Electronic)
IS  - 2001-3078 (Linking)
VI  - 1
DP  - 2012
TI  - Stable cell fate changes in marrow cells induced by lung-derived microvesicles.
LID - 10.3402/jev.v1i0.18163 [doi]
AB  - BACKGROUND: Interest has been generated in the capacity of cellular-derived 
      microvesicles to alter the fate of different target cells. Lung, liver, heart and 
      brain-derived vesicles can alter the genetic phenotype of murine marrow cells; 
      however, the stability of such changes and the mechanism of these changes remain 
      unclear. In the present work, we show that lung-derived microvesicles (LDMV) 
      alter the transcriptome and proteome of target marrow cells initially by mRNA and 
      regulator(s) of transcription transfer, but that long term phenotype change is 
      due solely to transfer of a transcriptional regulator with target cell. IN VIVO 
      STUDIES: Whole bone marrow cells (WBM) were co-cultured with LDMV (both isolated 
      from male C57BL/6 mice) or cultured alone (control). One week later, cultured WBM 
      was transplanted into lethally-irradiated female C57BL/6 mice. Recipient mice 
      were sacrificed 6 weeks later and WBM, spleens and livers were examined for the 
      presence of lung-specific gene expression, including surfactants A, B, C and D, 
      aquaporin-5, and clara cell specific protein, via real-time RT-PCR. 
      Immunohistochemistry was also performed on lungs to determine the number of 
      transplanted marrow-derived (Y chromosome+) type II pneumocytes (prosurfactant 
      C+). Mice transplanted with LDMV co-cultured WBM expressed pulmonary epithelial 
      cell genes in the cells of their bone marrow, livers and spleens and over 
      fivefold more transplanted marrow-derived Y+/prosurfactant C+cells could be found 
      in their lungs (vs. control mice). IN VITRO STUDIES: WBM (from mice or rats) was 
      cultured with or without LDMV (from mice or rats) for 1 week then washed and 
      cultured alone. WBM was harvested at 2-week intervals for real-time RT-PCR 
      analysis, using species-specific surfactant primers, and for Western Blot 
      analysis. Proteomic and microRNA microarray analyses were also performed on 
      cells. LDMV co-cultured WBM maintained expression of pulmonary epithelial cell 
      genes and proteins for up to 12 weeks in culture. Surfactant produced at later 
      time points was specific only to the species of the marrow cell in culture 
      indicating de novo mRNA transcription. These findings, in addition to the altered 
      protein and microRNA profiles of LDMV co-cultured WBM, support a stable 
      transcriptional mechanism for these changes. CONCLUSIONS: These data indicate 
      that microvesicle alteration of cell fate is robust and long-term and represents 
      an important new aspect of cellular biology.
FAU - Aliotta, Jason M
AU  - Aliotta JM
AD  - Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert 
      Medical School of Brown University, Providence RI 02903, USA ; Division of 
      Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, The Warren 
      Alpert Medical School of Brown University, Providence RI 02903, USA.
FAU - Pereira, Mandy
AU  - Pereira M
FAU - Li, Ming
AU  - Li M
FAU - Amaral, Ashley
AU  - Amaral A
FAU - Sorokina, Arina
AU  - Sorokina A
FAU - Dooner, Mark S
AU  - Dooner MS
FAU - Sears, Edmund H
AU  - Sears EH
FAU - Brilliant, Kate
AU  - Brilliant K
FAU - Ramratnam, Bharat
AU  - Ramratnam B
FAU - Hixson, Douglas C
AU  - Hixson DC
FAU - Quesenberry, Peter J
AU  - Quesenberry PJ
LA  - eng
GR  - P20 GM103468/GM/NIGMS NIH HHS/United States
GR  - K08 HL086868/HL/NHLBI NIH HHS/United States
GR  - R01 HL103726/HL/NHLBI NIH HHS/United States
GR  - P20 RR025179/RR/NCRR NIH HHS/United States
GR  - P20 GM103421/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20120416
PL  - United States
TA  - J Extracell Vesicles
JT  - Journal of extracellular vesicles
JID - 101610479
PMC - PMC3760634
OTO - NOTNLM
OT  - bone marrow cells
OT  - bone marrow transplant
OT  - lung
OT  - microvesicles
OT  - transcription factor
EDAT- 2012/01/01 00:00
MHDA- 2012/01/01 00:01
PMCR- 2012/04/16
CRDT- 2013/09/07 06:00
PHST- 2012/02/19 00:00 [received]
PHST- 2012/03/10 00:00 [revised]
PHST- 2012/03/12 00:00 [accepted]
PHST- 2013/09/07 06:00 [entrez]
PHST- 2012/01/01 00:00 [pubmed]
PHST- 2012/01/01 00:01 [medline]
PHST- 2012/04/16 00:00 [pmc-release]
AID - 18163 [pii]
AID - 10.3402/jev.v1i0.18163 [doi]
PST - epublish
SO  - J Extracell Vesicles. 2012 Apr 16;1. doi: 10.3402/jev.v1i0.18163. eCollection 
      2012.