George Church is thinking a lot about using regeneration as the key to treatments and keeping people healthy. Induced pluripotent stem cells “is where I’m putting almost all of my chips these days, because it combines many of my interests — genomics, sequencing, epigenetics, synthetic biology, stem cells,” Church adds. While much of the work so far has been done in rodents, he says that it’ll be years, not decades, until it is tested in people. “The only way people are going to get this is through some brave soul,” Church says. “It will start with a sick person, and they will end up getting well, possibly more well than before they got sick.” Read more in MIT’S Technology Review‘s Experimental Man.
Of the five “hottest” papers of 2009 in biology, three were published in NATURE, two in CELL. The topics are no surprise: genomics and stem cells. Click and read:
1. K. Takahashi, et al., “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,” Cell, 131: 861-72, 2007.
Citations this year: 520
Total citations to date: 886
Findings: This work from Shinya Yamanaka’s lab in Japan was the first to demonstrate that induced pluripotent stem (iPS) cells can be generated from adult human dermal fibroblasts. Previous efforts by the team showed that iPS cells could be derived from mouse somatic cells
2. K.A. Frazer, et al., “A second generation human haplotype map of over 3.1 million SNPs,” Nature, 449: 854-61, 2007.
Citations this year: 389
Total citations to date: 588
Findings: Since the sequencing of the human genome in 2003, the International HapMap Project has explored single nucleotide polymorphisms (SNPs) — differences in a single letter of the DNA — to study how these small variations affect the development of diseases and the body’s response to pathogens and drugs. HapMap I, the original report, placed one SNP at roughly every 5,000 DNA letters. The newest map, featured in this paper, sequenced an additional 2 million SNPs, increasing the map’s resolution to one SNP per kilobase. The additional detail allows scientists to more closely investigate patterns in SNP differences, especially in hotspot regions, or concentrated stretches of DNA.
3. A. Barski, et al., “High-resolution profiling of histone methylations in the human genome,” Cell, 129: 823-37, 2007.
Citations this year: 299
Total citations to date:: 560
Findings: This study looked at how histone modifications influence gene expression in more detail than previous attempts. Using a powerful sequencing tool called Solexa 1G, the researchers mapped more than 20 million DNA sequences associated with specific forms of histones, finding there were differences in methylation patterns between stem cells and differentiated T cells.
4. E. Birney, et al., “Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project, “Nature, 447: 799-816, 2007.
Citations this year: 267
Total citations to date: 618
Findings: The ENCODE project — ENCODE stands for the ENCyclopedia Of DNA Elements — set out to identify all functional elements in the human genome. After examining one percent of the genome, the paper revealed several new insights about how information encoded in the DNA comes to life in a cell.
5. A M. Wernig, et al., “In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state,” Nature 448: 318-24, 2007.
Citations this year: 237
Total citations to date: 512
Findings: Scientists successfully performed somatic-cell nuclear transfer (SCNT), producing stem cell lines and cloned animals for the first time using fertilized mouse eggs.
Friday Lecture Series
Stem Cells, Pluripotency and Nuclear Reprogramming
Rudolf Jaenisch, M.D.
Member, Whitehead Institute for Biomedical Research
Professor of Biology, Massachusetts Institute of Technology
Friday, January 30, 2009
3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)
Brambrink, T., R. Foreman, G. G. Welstead, C. J. Lengner, M. Wernig, H. Suh, and R. Jaenisch. 2008. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell. 2(2):151-159.
Hanna, J., S. Markoulaki, P. Schorderet, B. W. Carey, C. Beard, M. Wernig, MennoP Creyghton, et al. 2008. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell. 133(2):250-264.
Hochedlinger, K., and R. Jaenisch. 2006. Nuclear reprogramming and pluripotency. Nature. 441(7097):1061-1067.
Hockemeyer, D., F. Soldner, E. G. Cook, Q. Gao, M. Mitalipova, and R. Jaenisch. 2008. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell. 3(3):346-353.
Jaenisch, R., and R. Young. 2008. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 132(4):567-582.
Lewitzky, M., and S. Yamanaka. 2007. Reprogramming somatic cells towards pluripotency by defined factors. Current Opinion in Biotechnology. 18(5):467-473.
Mikkelsen, T. S., J. Hanna, X. Zhang, M. Ku, M. Wernig, P. Schorderet, B. E. Bernstein, R. Jaenisch, E. S. Lander, and A. Meissner. 2008. Dissecting direct reprogramming through integrative genomic analysis. Nature. 454(7200):49-55.
Wernig, M., C. J. Lengner, J. Hanna, M. A. Lodato, E. Steine, R. Foreman, J. Staerk, S. Markoulaki, and R. Jaenisch. 2008. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nature Biotechnology. 26(8):916-924.
Wernig, M., J. -P Zhao, J. Pruszak, E. Hedlund, D. Fu, F. Soldner, V. Broccoli, M. Constantine-Paton, O. Isacson, and R. Jaenisch. 2008. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America. 105(15):5856-5861.
Yamanaka, S. 2008. Pluripotency and nuclear reprogramming. Philosophical Transactions of the Royal Society B: Biological Sciences. 363(1500):2079-2087.
Monday Seminar Series
Genetic Dissection of Pluripotency in
Human Embryonic Stem Cells
Ali H. Brivanlou PhD
Robert and Harriet Heilbrunn Professor
The Rockefeller University
Monday, November 3, 2008
Welch Hall Level Two Refreshments 3:45 Lecture 4:00
Noggle, SA; D. James and AH Brivanlou. 2005. A molecular basis for human embryonic stem cell pluripotency. Stem cell reviews. 1(2):111-118.
Schwartz, PH et al. 2008. Differentiation of neural lineage cells from human pluripotent stem cells. Methods. 45(2):142-158
Stewart, MH; SC BEndell and M. Bhatia. 2008. Deconstructing human embryonic stem cell cultures: niche regulation of self-renewal and pluripotency. Journal of molecular medicine. 86(8):875-886
Todeur, S. et al. 2008. Biology and potentialities of of human embryonic stem cells. Annales de biologie clinique. 66(3):241-247
Ohtsuka, S. and S. Dalton. 2008. Molecular and biolgoical properties of pluripotent embryonic stem cells. Gene therapy. 15(2):74-81
Oliveri, RS. 2007. Epigenetic dedifferentiation of somatic cells into pluripotency: cellular alchemy in the age of regenerative medicine? Regenerative medicine. 2(5):795-816
Darr, H. and N. Benvenisry. 2006. Human embryonic stem cells: the battle between self-renewal and differentiation. Regenerative medicine. 1(3):327-325
Avery, S.; K. Inniss and H. Moore. 2006. The regulation of self-renewal in human embryonic stem cells. Stem cells and development. 15(5):729-740.
Skottman, H.; MS Dilber and O. Hovatta. 2006. The derivation of clnical-grade human embryonic stem cell lines. FEBS Letters. 580(12):2875-2878