Profilaksa DVT kod velikih ortopedskih operacija - Depol ...

20 - 22 September 2012, Opatija, Croatia
STEM CELLS AND PREDICTION OF PHENOTYPE THROUGH
TRANSCRIPTOME DECONVOLUTION
Carmen Terzic, Mayo Clinic, Rochester, United States
Genomic perturbations that challenge normal signaling at the pluripotent stage may trigger unforeseen ontogenic
aberrancies. Anticipatory systems biology identification of transcriptome landscapes that underlie latent
phenotypes would offer molecular diagnosis before the onset of symptoms. Bioinformatic surveillance of calreticulin-null
stem cells, a monogenic insult model, diagnosed a disruption in transcriptome dynamics, which re-prioritized
essential cellular functions. Calreticulin-calibrated signaling axes were uncovered, and network-wide cartography
of undifferentiated stem cell transcripts suggested cardiac manifestations. Calreticulin-deficient stem
cell-derived cardiac cells verified disorganized sarcomerogenesis, mitochondrial paucity, and cytoarchitectural
aberrations to validate calreticulin-dependent network forecasts. Furthermore, magnetic resonance imaging and
histopathology detected a ventricular septal defect, revealing organogenic manifestation of calreticulin deletion.
Thus, bioinformatic deciphering of a primordial calreticulin-deficient transcriptome decoded at the pluripotent
stem cell stage a reconfigured multifunctional molecular registry to anticipate predifferentiation susceptibility
toward abnormal cardiophenotype.
Oral
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