Home » Newsroom » Research Newsletter » Research Newsletter - September 2008

Research Newsletter - September 2008

Spotlight

In an article paper published in Nature, HSCI Co-Director Douglas Melton and his team report the identification a specific combination of three transcription factors that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells.

In vivo reprogramming of adult pancreatic exocrine cells to beta-cells

Abstract:

One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.

Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008 Aug 27. Read Paper.

Scientific Papers

Review and Commentary

  • Akashi T, Shigematsu H, Hamamoto Y, Iwasaki H, Yatoh S, Bonner-Weir S, Akashi K, Weir GC. Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice. Diabetes Metab Res Rev. 2008 Aug 26. Read Abstract.
  • Dessaud E, McMahon AP, Briscoe J. Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development. 2008 Aug;135(15):2489-503. Read Abstract.
  • Kim CF, Dirks PB. Cancer and stem cell biology: how tightly intertwined? Cell Stem Cell. 2008 Aug 7;3(2):147-50. Read Abstract.
  • Kreidberg JA, Hartwig S. Wilms' tumor-1: a riddle wrapped in a mystery, inside a kidney. Kidney Int. 2008 Aug;74(4):411-2. Read Abstract.
  • Ofran Y, Ritz J. Targets of tumor immunity after allogeneic hematopoietic stem cell transplantation. Clin Cancer Res. 2008 Aug 15;14(16):4997-9. Read Abstract.
  • Podesser BK, Bauer M, Liao R. Evolving cell-based therapies for heart failure patients. Curr Treat Options Cardiovasc Med. 2008 Aug;10(4):358-67. Read Abstract.
  • Scholl C, Gilliland DG, Fr√ɬ∂hling S. Deregulation of signaling pathways in acute myeloid leukemia. Semin Oncol. 2008 Aug;35(4):336-45. Read Abstract.
  • Sosnovik DE, Nahrendorf M, Weissleder R. Targeted imaging of myocardial damage. Nat Clin Pract Cardiovasc Med. 2008 Aug;5 Suppl 2:S63-70. Read Abstract.

Blood

  • Brown JR, Levine RL, Thompson C, Basile G, Gilliland DG, Freedman AS. Systematic genomic screen for tyrosine kinase mutations in CLL. Leukemia. 2008 Aug 28. Read Abstract.
  • Kawamata N, Ogawa S, Yamamoto G, Lehmann S, Levine RL, Pikman Y, Nannya Y, Sanada M, Miller CW, Gilliland DG, Koeffler HP. Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray. Exp Hematol. 2008 Aug 22. Read Abstract.
  • Larsson J, Ohishi M, Garrison B, Aspling M, Janzen V, Adams GB, Curto M, McClatchey AI, Schipani E, Scadden DT. Nf2/merlin regulates hematopoietic stem cell behavior by altering microenvironmental architecture. Cell Stem Cell. 2008 Aug 7;3(2):221-7. Read Abstract.
  • Milsom MD, Jerabek-Willemsen M, Harris CE, Schambach A, Broun E, Bailey J, Jansen M, Schleimer D, Nattamai K, Wilhelm J, Watson A, Geiger H, Margison GP, Moritz T, Baum C, Thomale J, Williams DA. Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells. Cancer Res. 2008 Aug 1;68(15):6171-80. Read Abstract.

Cancer

  • Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, Papa A, Nardella C, Cantley LC, Baselga J, Pandolfi PP. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008 Aug 21. Read Abstract.
  • Chen S, Ndhlovu LC, Takahashi T, Takeda K, Ikarashi Y, Kikuchi T, Murata K, Pandolfi PP, Riccardi C, Ono M, Sugamura K, Ishii N. Co-inhibitory roles for glucocorticoid-induced TNF receptor in CD1d-dependent natural killer T cells. Eur J Immunol. 2008 Aug;38(8):2229-40. Read Abstract.
  • Nardella C, Chen Z, Salmena L, Carracedo A, Alimonti A, Egia A, Carver B, Gerald W, Cordon-Cardo C, Pandolfi PP. Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events. Genes Dev. 2008 Aug 15;22(16):2172-7. Read Abstract.
  • Sch√ɬºller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, Huillard E, Sun T, Ligon AH, Qian Y, Ma Q, Alvarez-Buylla A, McMahon AP, Rowitch DH, Ligon KL. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008 Aug 12;14(2):123-34. Read Abstract.
  • Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008 Aug 20. Read Abstract.
  • Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. A paracrine requirement for hedgehog signalling in cancer. Nature. 2008 Aug 27. Read Abstract.

Cardiovascular System

  • Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Marks MH, Walker AJ, Seki T, Oh SP, Lu JT, Sumners C, Raizada MK, Horikoshi N, Weinberg EO, Yasui K, Ikeda Y, Chien KR, Kasahara H. Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction Defects. Circ Res. 2008 Aug 8. Read Abstract.
  • Zhou B, Gise AV, Ma Q, Rivera-Feliciano J, Pu WT. Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochem Biophys Res Commun. 2008 Aug 21. Read Abstract.

Developmental Biology

  • Boag PR, Atalay A, Robida S, Reinke V, Blackwell TK. Protection of specific maternal messenger RNAs by the P body protein CGH-1 (Dhh1/RCK) during Caenorhabditis elegans oogenesis. J Cell Biol. 2008 Aug 11;182(3):543-57. Read Abstract.
  • Caron SJ, Prober D, Choy M, Schier AF. In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis. Development. 2008 Aug 28. Read Abstract.
  • Ebralidze AK, Guibal FC, Steidl U, Zhang P, Lee S, Bartholdy B, Jorda MA, Petkova V, Rosenbauer F, Huang G, Dayaram T, Klupp J, O'Brien KB, Will B, Hoogenkamp M, Borden KL, Bonifer C, Tenen DG. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes Dev. 2008 Aug 1;22(15):2085-92. Read Abstract.
  • Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, Goetz R, Mohammadi M, Kuro-O M, Olsen BR, Lanske B. FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. J Cell Biol. 2008 Aug 11;182(3):459-65. Epub 2008 Aug 4. Read Abstract.
  • Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-Specific Induced Pluripotent Stem Cells. Cell. 2008 Aug 6. Read Abstract.

Diabetes

  • Larade K, Jiang Z, Zhang Y, Wang W, Bonner-Weir S, Zhu H, Bunn HF. Loss of NCB5or results in impaired fatty acid desaturation, lipoatrophy and diabetes. J Biol Chem. 2008 Aug 5. Read Abstract.
  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008 Aug 27. Read Abstract.

Genetics and Genomics

  • Chiara Manzini M, Gleason D, Chang BS, Sean Hill R, Barry BJ, Partlow JN, Poduri A, Currier S, Galvin-Parton P, Shapiro LR, Schmidt K, Davis JG, Basel-Vanagaite L, Seidahmed MZ, Salih MA, Dobyns WB, Walsh CA. Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East. Hum Mutat. 2008 Aug 27. Read Abstract.

Imaging

  • "Korosoglou G, Weiss RG, Kedziorek DA, Walczak P, Gilson WD, Sch√ɬ§r M, Sosnovik DE, Kraitchman DL, Boston RC, Bulte JW, Weissleder R, Stuber M. Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using ""positive contrast"" magnetic resonance imaging. J Am Coll Cardiol. 2008 Aug 5;52(6):483-91." Read Abstract.
  • Gounaris E, Tung CH, Restaino C, Maehr R, Kohler R, Joyce JA, Plough HL, Barrett TA, Weissleder R, Khazaie K. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth. PLoS ONE. 2008 Aug 13;3(8):e2916. Read Abstract.

Immunology

  • Gavanescu I, Benoist C, Mathis D. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients. Proc Natl Acad Sci USA. 2008 Sep 2;105(35):13009-14. Epub 2008 Aug 28. Read Abstract.
  • Haining WN, Ebert BL, Subrmanian A, Wherry EJ, Eichbaum Q, Evans JW, Mak R, Rivoli S, Pretz J, Angelosanto J, Smutko JS, Walker BD, Kaech SM, Ahmed R, Nadler LM, Golub TR. Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells. J Immunol. 2008 Aug 1;181(3):1859-68. Read Abstract.

Nervous System

  • Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F. Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons. Curr Biol. 2008 Aug 5;18(15):1133-7. Read Abstract.

Pulmonary System

  • Dovey JS, Zacharek SJ, Kim CF, Lees JA. Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion. Proc Natl Acad Sci USA. 2008 Aug 19;105(33):11857-62. Epub 2008 Aug 12. Read Abstract.

Renal System

  • Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, McMahon AP. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008 Aug 7;3(2):169-81. Read Abstract.

Reproductive System

  • Szotek PP, Chang HL, Brennand K, Fujino A, Pieretti-Vanmarcke R, Lo Celso C, Dombkowski D, Preffer F, Cohen KS, Teixeira J, Donahoe PK. Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics. Proc Natl Acad Sci USA. 2008 Aug 26;105(34):12469-73. Epub 2008 Aug 18. Read Abstract.

Tissue Engineering

  • Duailibi SE, Duailibi MT, Zhang W, Asrican R, Vacanti JP, Yelick PC. Bioengineered dental tissues grown in the rat jaw. J Dent Res. 2008 Aug;87(8):745-50. Read Abstract.