Tlsty: hESCs do not express CD73; no effect on SON expression in hESCs #ncistg14

11:25am March 21st 2014 via Hootsuite

Tlsty: CD73 inhibition: a 5' nucleotidase to create adenosine. CD73 knockdown affects SON #ncistg14

11:24am March 21st 2014 via Hootsuite

Tlsty: ePS are rare, 'reserve cells'. Found in other tissues (pancreas ePS cells can create ectodermal tissue) #ncistg14

11:21am March 21st 2014 via Hootsuite

Tlsty: ePS cells do not challenge concept of tissue-specific stem cells (exist side-by-side). May contribute to wound healing #ncistg14

11:20am March 21st 2014 via Hootsuite

Tlsty: Criteria of pleuripotency 2004 Cell ref: http://t.co/mZJUIeOjy4 Validated independently, indistinguishable #ncistg14

11:19am March 21st 2014 via Hootsuite

Tlsty: Telomerase activity confirms mortality, also normal karyotype after 59 doublings #ncistg14

11:18am March 21st 2014 via Hootsuite

Tlsty: ePS are mortal and genomically intact. Can be expanded - ~59 doublings; after 120d culture majority of cells in G1 #ncistg14

11:17am March 21st 2014 via Hootsuite

Tlsty: ePS compared to hESC and iPS and mesenchymal stem cells and mammary stem cells: ePS are different in expression, markers #ncistg14

11:16am March 21st 2014 via Hootsuite

Tlsty: Forensic analysis (STR) confirms lineage of tissue of ePS #ncistg14

11:15am March 21st 2014 via Hootsuite

Tlsty: R1 fx co-expresses pluripotency markers Oct3/4, Sox2, Nanog. Called ePS (endogenous Plastic Somatic cells) #ncistg14

11:14am March 21st 2014 via Hootsuite

Tlsty: All R1 cells were not cultured. Were they homogeneous however? A single cell does have the lineage diff. ability #ncistg14

11:14am March 21st 2014 via Hootsuite

Tlsty: R1 can create teratomas, three main derivatives and others; R2-R4 no growths. R1 cells are not malignant #ncistg14

11:12am March 21st 2014 via Hootsuite

Tlsty: Most difficult - endodermal lineage using published protocols; SOX17 and FOXA2, then pancreatic lineage #ncistg14

11:10am March 21st 2014 via Hootsuite

Tlsty: R1 also differentiate into CD31-pos HUVEC cells; R1 can also differentiate into cardiomyocytes -both molecular + functional #ncistg14

11:09am March 21st 2014 via Hootsuite

Tlsty: These R1 cells can produce glial and neural progenitor cells, even adipocytes that produce cell-type spec genes #ncistg14

11:08am March 21st 2014 via Hootsuite

Tlsty: Novel marker not used before for stem cell selection; lineage promiscuity, cells with great potential. #ncistg14

11:07am March 21st 2014 via Hootsuite

Tlsty: Showed R1 rare cells can recapitulate the human mammary gland in a murine host. #ncistg14

11:06am March 21st 2014 via Hootsuite

Tlsty: Markers were CD90 / CD73; R1 to R4 quadrants as a fn of passage: R1 is 0.15% of population, can reconstitute tissue #ncistg14

11:05am March 21st 2014 via Hootsuite

Tlsty: FACS to isolate sub-populations from >100 healthy donors. 2013 PNAS ref: http://t.co/RUZHU8byCj #ncistg14

11:04am March 21st 2014 via Hootsuite

Tlsty: Chose Thy-1, 5-NED epitopes for membrane-assoc'd markers of +/- p16 in healthy mammary tissues #ncistg14

11:02am March 21st 2014 via Hootsuite

Tlsty: Stress-tolerant cells (p16 down) isolated, using exp profiling, found cell-surface markers toggled by p16 100-fold #ncistg14

11:01am March 21st 2014 via Hootsuite

Tlsty: Repressed p16: bypasses senescence, also uncouples centrosome duplication, confers epigen. plasticity #ncistg14

10:59am March 21st 2014 via Hootsuite

Tlsty: Arrest vs proliferation - what controls it? p16 repression can be mutated or reversible #ncistg14

10:58am March 21st 2014 via Hootsuite

Tlsty: ER+/- cells: A spectrum of resistance Transcription, translation, protein degradation, protein modifications: all fluctuate#ncistg14

10:56am March 21st 2014 via Hootsuite

Tlsty: Stochasticity - fluctuating protein levels, only seen at the single-cell level. Two different phenotypes from a single cell #ncistg14

10:55am March 21st 2014 via Hootsuite

Tlsty: Non-genetic hetergeneity, probably at the epigenome level. Adaptation, differentiation, ecology. #ncistg14

10:54am March 21st 2014 via Hootsuite

Tlsty: Characteristic of a complex adaptive system - self-organizing, system 'learns'... #ncistg14

10:52am March 21st 2014 via Hootsuite

Tlsty: Non-mutagenic process caused by physical and chemical stresses, causing hetergeneity #ncistg14

10:52am March 21st 2014 via Hootsuite

Thea Tlsty, University of California San Francisco: Stochastic Cellular States Associated with Malignancy #ncistg14

10:51am March 21st 2014 via Hootsuite

Markowitz: Risk allele of a PGDH promoter SNP to colorectal cancer; located in a small LD block Ref: http://t.co/BFckkGpaul #ncistg14

10:12am March 21st 2014 via Hootsuite

Markowitz: Nurses Health Study, from normal colon that went on to develop cancer, affect of aspirin Ref: http://t.co/AEXP7rXEDv #ncistg14

10:09am March 21st 2014 via Hootsuite

Markowitz: COX-2, Cyclin D1 induction, leading to colonic neoplasia, suppressed by 15-PGDH PNAS: http://t.co/l2955TfGX3 #ncistg14

10:04am March 21st 2014 via Hootsuite

Markowitz: Biochemistry of prostaglandins, lots of biology to signaling, from growth, migration, anti-apoptosis, angiogenesis #ncistg14

9:57am March 21st 2014 via Hootsuite

Markowitz: For CRC what's downstream? TGFb up-regulated, then colon cancers turn down? One gene: 15-PGDH #ncistg14

9:56am March 21st 2014 via Hootsuite

Markowitz: Work from '95 - '99: RII gene targeted with SMAD complex. Vogelstein's 2013 science review figure #ncistg14

9:55am March 21st 2014 via Hootsuite

Markowitz:Defect in mismatch repair, hotspot in TGF-beta RII mutations #ncistg14

9:53am March 21st 2014 via Hootsuite

Markowitz: 15-PDDH a metabolic tumor suppressor pathway that regulates colon cancer dev., suscept., & chemoprev. with NSAIDS #ncistg14

9:52am March 21st 2014 via Hootsuite

Sanford Markowitz, Case Western Reserve University: Genetic Pathways in Colon Cancer #ncistg14

9:51am March 21st 2014 via Hootsuite

Swanton:Two principles: decipher mechanisms of cancer diversity, and improve cancer selection pressures (targeting drivers) #ncistg14

9:45am March 21st 2014 via Hootsuite

Swanton: Then genome doubled, then another round of chrom instability, #ncistg14

9:38am March 21st 2014 via Hootsuite

Swanton: NSCLC shared mut's illustrating a genome doubling event, EGFR RB1, PS3, all share instability. #ncistg14

9:38am March 21st 2014 via Hootsuite

Swanton: Trunk drivers, setting up a trial targeting clonally dominant drivers early on #ncistg14

9:36am March 21st 2014 via Hootsuite

Swanton: WES before drug therapy, and then focused gene panel after if therapy fails. See branched evolution, showing 8 samples #ncistg14

9:36am March 21st 2014 via Hootsuite

Swanton:Tracking non-small cell lung Cancer Evol through therapy ("TRACERx") #ncistg14

9:35am March 21st 2014 via Hootsuite

Swanton: Driver vs. passenger mutation profile terribly complex. There is a tumor sampling bias. #ncistg14

9:34am March 21st 2014 via Hootsuite

Swanton: 6 of 120 mutations occurring in only 2 genes, a SWI/SNF chromatin remodeling complex #ncistg14

9:30am March 21st 2014 via Hootsuite

Swanton: Then use a model to predict the 'trunk' mutation, looking at SETD2 changes across clonal evolution #ncistg14

9:29am March 21st 2014 via Hootsuite

Swanton: (5% vs. 40% was for P53) #ncistg14

9:28am March 21st 2014 via Hootsuite

Swanton: Est of driver prevalence from a single vs multiple biopsy: marked difference. 5% vs 40% #ncistg14

9:28am March 21st 2014 via Hootsuite

Swanton: Metastatic sites evolved through chromosomal instability, assoc'd with poor outcome. #ncistg14

9:25am March 21st 2014 via Hootsuite