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iPS cells, or induced pluripotent stem cells, are adult cells that have been artificially reprogrammed to an embryonic stem cell-like state through the expression of specific genes. Nobel Prize winner Shinya Yamanaka conducted research demonstrating that mouse fibroblasts could be reprogrammed into iPS cells through the use of transcription factors. While iPS cells show promise for regenerative medicine applications, current research is focused on addressing issues such as variability in gene expression and DNA methylation between iPS cell lines as well as developing methods to create iPS cells without integrating vectors that could cause mutations.
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7 ipsc 3:5:13
- 1. I-PS CELLS Capt RishiPokhrel JOURNAL CLUB
- 2. iPS cell ‘Induced pluripotentstem cell is a type of pluripotent stem cell artificially derived from a non-pluripotent cell - typically an adult somatic cell - by inducing a "forced" expression of specific genes’. Baker, Monya (2007-12-06). "Adult cells reprogrammed to pluripotency, without tumors". Nature Reports Stem Cells. doi:10.1038/stemcells.2007.124
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- 4. President of theInternational Society for Stem Cell Research (ISSCR). MBBS MD (1987) Ph. D (1993) Residency in Orthopedic surgery Post doctoral fellowship in Cardiovascular disease Professor of anatomy University of California, San Francisco, USA
- 5. Nobel prize awardedfor • Generation of induced pluripotent stem cells from adult mouse fibroblasts (2006) • Closedly resembled embryonic stem cells (in vivo equivalent of blastocyst) • iPSC were pluripotent – could generate whole iPSC mice • iPSC cells from human adult fibroblasts for the first time (2007) • Initially used 24 transcription factors for inducing pluri-potency • Successful in narrowing down the number of factors to just 4 Sox2, Oct4, Klf 4 and c-Myc
- 7. Yamanaka S Cell stemcell June 14, 2012 Volume 10, No 6 Page no 678-684
- 9. Literature review • Stemcells • Transcription factors
- 10. • Stem cells •Application • Problem
- 11. Transcription factor A regulatoryprotein that binds to DNA and affects the transcription of specific genes.
- 12. Introduction iPSC: Past, Presentand future
- 13. How was iPSCpossible? • Reprogramming by nuclear transfer • Tadpoles from unfertilized eggs that received nucleus from intestinal cells of adult frogs (Gurdon J 1962) • Cloning of Dolly (Wilmut W 1997) • Adult somatic cells contain all genetic information • Oocyte contain factors that can reprogram somatic cell nuclei, so do ESC (Tada T 2001) 1Past
- 14. How was iPSCpossible? • Discovery of transcription factors – Genes of drosophila coding for antenna could form legs when ‘antennapeda’ was introduced (Schneuwly 1987) – Mammalian fibroblasts converted to myocyte using MyoD (Davis 1987) 2
- 15. How was iPSCpossible? • Generation of ESC, mouse (Evans 1981), human (Thomson 1988) and culture media • Long term maintenance of pluripotency using LIF (Smith 1988) • Optimal cultural conditions with bFGF 3
- 16. • iPSC :simplicity and reproducibility • Poor efficacy: success rate 1% (?) • Integrated vectors used for introducing transcription factors -> retroviruses, can cause mutagenesis & other adverse effects • Use of non-integrated vectors: plasmid, Sendai virus, adenovirus, synthetic RNA and proteins • Technology development -> applications Present
- 17. Current works focusedin Regenerative medicine –Parkinson's disease –Platelet deficiency –Spinal cord injury –Macular degeneration Future
- 18. Disease models • Patientderived iPSC used for testing of drugs & toxins • Found useful for creating models of late onset diseases like Parkinson’s, Alzheimer’s, Schizophrenia • Analysis of disease mechanisms
- 19. Use in animals •Genetic engineering • Production of deficient proteins e.g. enzymes • Preservation or recreation of endangered or extinct animals
- 20. Direct reprogramming • Invivo conversion of exocrine pancreatic cells to endocrine using 3 transcription factors (Zhou 2008) • In vitro conversion of adult mature fibroblasts to neural cells, hepatocyte, cardiomyocyte or hematopoietic progenitor cells • Problem: source of cells? A step ahead
- 21. iPSC Vs ESC •Similar and different Source of tissue – Culture medium – Source of clone e.g. labs – Vectors used – Both are basically artificial cells
- 23. Dark side • Variationin – gene expression – DNA methylation – Pluripotent potential – Somatic mutations – Copy number variations – Immunogenicity
- 24. So is itjust another hoax? DARK SIDE UNDER ATTACK FLAWED TROUBLESOME GROWING PAINS
- 25. Not really • Geneticdefects preexisted in source cells • Cloning magnified the defects • Immunogenicity is very weak - its effects nil in animal experiments • ESC not gold standard for comparisons of iPSC
- 26. Conclusions • iPSC technologyready for applications • Necessity of establishment of in-advance stocks of clones • Source of tissue: healthy donors, cord blood, HLA homozygous donors
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Editor's Notes
- #2 In this journal club I intend to discuss a review article discussing iPSC, which will broaden our knowledge about contemporary research in anatomy and cell biology.At the end of session one should be able to write at least a short note in iPSC.
- #3 To start with…Before we proceed to the article of discussion itself.. A brief note on how how came across this article and why we should know about iPSC .Baker, Monya (2007-12-06). "Adult cells reprogrammed to pluripotency, without tumors". Nature Reports Stem Cells. doi:10.1038/stemcells.2007.124
- #4 Chinese? Nepalese? Naaa Japanese. He had a very interesting and unique career.
- #5 Born in 1962, Osaka , JapanHe was regarded as a lousy surgeon by his colleagues and was nicknamed "Jamanaka” a Japanese word for ‘obstacle’ after he took more than an hour to remove a benign tumor which usually takes not more than 10 minutes. Interestingly, one reason he was admitted into his first stem cell research because of his can do attitude.
- #6 Like anybody else, I was more curious than before and wanted to know more about iPSC. I turned to PubMed.
- #7 Within 4-5 years around 5 thousand articles were published on iPSC.
- #8 I came across what I was looking for..
- #9 A review article written by the master himselfBefore we discuss the article it would be a good idea to go through some terms that we need to understand.
- #11 Alexander Maksimov 1908 postulated hematopoetic stem cellsJoseph Altman and Gopal Das1960 Vs CajalTill and McCulloch 1963, hematopoeticSo there was this need for stem cells that were not antigenic and the best candidate for this was stem cell derived from the patient or subject himself.Another term is transcription factor.
- #12 These are inserted into cell and then into nucleus using vectors most common of which are retrovirus. Retroviruses remain in cell thereafter (Integrated)With this background, now lets proceed to the article.
- #13 First we will discuss the past? What made scientists to think that somatic or terminally differentiated cells could be reverted back to stem cells .There were 3 streams of researches which cumulated into scientists believe that iPSC were possible.
- #14 ESC: extra embryonic stem cellsDonar cell taken from mammary gland.Dolly Parton
- #16 LIF: leukemia inhibiting factorbFGF: basic fibroblast growth factor
- #17 iPSC are being generated and researched by labs throughout the world owing to its …..but has been criticized for ,,,,due to not very clearly known reasons.
- #18 What will the audience be able to do after this training is complete?Briefly describe each objective and how the audience will benefit from this presentation.
- #21 If somatic cells can be converted to stem cells why cant one somatic cell type converted to another somatic cell type e.g. hepatocyte to cardiomyocyte?
- #29 Use a section header for each of the topics, so there is a clear transition to the audience.