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Research Newsletter - January 2007

Spotlight

In a research paper published in Science, investigators from the Harvard Stem Cell Institute, Children's Hospital Boston, Harvard Medical School, Brigham and Women's Hospital and Massachusetts General Hospital describe how mouse embryonic stem cells can be generated by parthenogenesis.

Histocompatible Embryonic Stem Cells by Parthenogenesis

In this study, George Daley and colleagues used unfertilized eggs of mice to create parthenogenetic embryonic stem cells. Parthenogenesis is a method of reproduction, common in plants and in some animals, in which the female can generate offspring without the contribution of a male. It doesn't normally occur in mice, but the team was able to induce unfertilized mouse eggs to develop through a series of chemical treatments, then generate embryonic stem cells.

Next, they identified those embryonic stem cells that shared with the egg donor the genes responsible for tissue matching, called the major histocompatibility complex (MHC). When they injected these selected embryonic stem cells into MHC-matched mice, a variety of specialized tissues formed, with no rejection and no need to suppress the recipients' immune system.

"This technique, if proven effective in humans, offers an efficient way of generating customized stem cell lines from women," says Daley. "It would eliminate tissue matching and tissue rejection problems, a major obstacle to successful tissue transplantation."

However, there are several potential limitations to embryonic stem cells generated by parthenogenesis. First, since parthenogenetic embryonic stem cells are made from eggs, the technique is only applicable to females. Also embryonic stem cells created through parthenogenesis have altered expression of imprinted genes, which has been linked with cancer and poor growth in some tissues. In addition, embryonic stem cells created through parthenogenesis may have some regions of their genome that contain duplicated copies of mutant genes that have been linked with malignancies or abnormal tissue growth.

"Right now this technique is useful for basic research, but we are hopeful that parthenogenetic cells might prove useful for therapies," Daley says. "Our cells produce normal tissues in mice, and there is a report in the clinical literature of a human patient whose blood was derived entirely from parthenogenetic cells. However, we'll have to demonstrate the safety and durability of cells derived from parthenogenetic embryonic stem cells before we could imagine any clinical use."

Daley's laboratory at Children's Hospital Boston is now trying to replicate its results with human eggs.

Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible Embryonic Stem Cells by Parthenogenesis. Science. 2006 Dec 14. Read Abstract.

Scientific Papers

Review and Commentary

  • Grimm J, Kircher MF, Weissleder R. Cell tracking : Principles and applications. Radiologe. 2007 Jan;47(1):25-33. German. Read Abstract.
  • Ihle JN, Gilliland DG. Jak2: normal function and role in hematopoietic disorders. Curr Opin Genet Dev. 2007 Feb;17(1):8-14. Read Abstract.
  • Levine RL, Gilliland DG. JAK-2 mutations and their relevance to myeloproliferative disease. Curr Opin Hematol. 2007 Jan;14(1):43-7. Review. Read Abstract.
  • Nahrendorf M, Weissleder R. Advances in cardiovascular medicine through molecular imaging. Radiologe. 2007 Jan;47(1):18-24. German. Read Abstract.
  • Sears C, Armstrong SA. Microarrays to identify new therapeutic strategies for cancer. Adv Cancer Res. 2007;96:51-74. Review. Read Abstract.
  • Wagers AJ. Wnt not, waste not. Cell Stem Cell. 2008 Jan 10;2(1):6-7. Read Abstract.

Blood

  • Tissing WJ, Den Boer ML, Meijerink JP, Menezes RX, Swagemakers S, van der Spek PJ, Sallan SE, Armstrong SA, Pieters R. Genome-wide identification of prednisolone-responsive genes in acute lymphoblastic leukemia cells. Blood. 2007 Jan 11; Read Abstract.

Cancer

  • Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007 Jan;11(1):83-95. Read Abstract.
  • Costa DB, Li S, Kocher O, Feins RH, Keller SM, Schiller JH, Johnson DH, Tenen DG, Halmos B. Immunohistochemical analysis of C/EBPalpha in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590. Lung Cancer. 2007 Jan 17; Read Abstract.
  • Nakazawa Y, Suzuki M, Manabe N, Yamada T, Kihara-Negishi F, Sakurai T, Tenen DG, Iwama A, Mochizuki M, Oikawa T. Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression. Oncogene. 2007 Jan 8; Read Abstract.
  • Shepard JL, Amatruda JF, Finkelstein D, Ziai J, Finley KR, Stern HM, Chiang K, Hersey C, Barut B, Freeman JL, Lee C, Glickman JN, Kutok JL, Aster JC, Zon LI. A mutation in separase causes genome instability and increased susceptibility to epithelial cancer. Genes Dev. 2007 Jan 1;21(1):55-9. Read Abstract.
  • Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C, Armstrong SA, Passegue E, Depinho RA, Gilliland DG. FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress. Cell. 2007 Jan 26;128(2):325-339. Read Abstract.
  • Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T. Restoration of p53 function leads to tumour regression in vivo. Nature. 2007 Jan 24; Read Abstract.

Cardiovascular System

  • Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007 Jan 23;115(3):377-86. Read Abstract.
  • Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007 Jan;117(1):195-205. Read Abstract.

Developmental Biology

  • Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, McMahon AP, Kopan R. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007 Feb;134(4):801-11. Read Abstract.
  • Gritli-Linde A, Hallberg K, Harfe BD, Reyahi A, Kannius-Janson M, Nilsson J, Cobourne MT, Sharpe PT, McMahon AP, Linde A. Abnormal hair development and apparent follicular transformation to mammary gland in the absence of hedgehog signaling. Dev Cell. 2007 Jan;12(1):99-112. Read Abstract.
  • Hultman KA, Bahary N, Zon LI, Johnson SL. Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a. PLoS Genet. 2007 Jan 26;3(1):e17. Read Abstract.
  • Matsuda T, Cepko CL. Controlled expression of transgenes introduced by in vivo electroporation. Proc Natl Acad Sci USA. 2007 Jan 16;104(3):1027-32. Read Abstract.
  • Neal J, Takahashi M, Silva M, Tiao G, Walsh CA, Sheen VL. Insights into the gyrification of developing ferret brain by magnetic resonance imaging. J Anat. 2007 Jan;210(1):66-77. Read Abstract.
  • Stanger BZ, Tanaka AJ, Melton DA. Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature. 2007 Jan 28; Read Abstract.

Diabetes

  • Rodacki M, Svoren B, Butty V, Besse W, Laffel L, Benoist C, Mathis D. Altered natural killer cells in type 1 diabetic patients. Diabetes. 2007 Jan;56(1):177-85. Read Abstract.
  • Weir GC, Bonner-Weir S. A dominant role for glucose in beta cell compensation of insulin resistance. J Clin Invest. 2007 Jan;117(1):81-3. Read Abstract.

Imaging

  • Izmailova ES, Paz N, Alencar H, Chun M, Schopf L, Hepperle M, Lane JH, Harriman G, Xu Y, Ocain T, Weissleder R, Mahmood U, Healy AM, Jaffee B. Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis Rheum. 2007 Jan;56(1):117-28. Read Abstract.
  • McCarthy JR, Weissleder R. Model Systems for Fluorescence and Singlet Oxygen Quenching by Metalloporphyrins. ChemMedChem. 2007 Jan 23; Read Abstract.

Immunology

  • Nguyen LT, Jacobs J, Mathis D, Benoist C. Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum. 2007 Jan 30;56(2):509-520 Read Abstract.

Nervous System

  • Chang BS, Duzcan F, Kim S, Cinbis M, Aggarwal A, Apse KA, Ozdel O, Atmaca M, Zencir S, Bagci H, Walsh CA. The role of RELN in lissencephaly and neuropsychiatric disease. Am J Med Genet B Neuropsychiatr Genet. 2007 Jan 5;144(1):58-63. Read Abstract.
  • Hedlund E, Pruszak J, Ferree A, Vinuela A, Hong S, Isacson O, Kim KS. Selection of embryonic stem cell derived eGFP+ dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations. Stem Cells. 2007 Jan 18; Read Abstract.

Renal System

  • Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, Mackinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. Urinary N-Acetyl-{beta}-(D)-Glucosaminidase Activity and Kidney Injury Molecule-1 Level Are Associated with Adverse Outcomes in Acute Renal Failure. J Am Soc Nephrol. 2007 Jan 31; Read Abstract.

Skeletal System

  • "Ueki Y, Lin CY, Senoo M, Ebihara T, Agata N, Onji M, Saheki Y, Kawai T, Mukherjee PM, Reichenberger E, Olsen BR. Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 ""cherubism"" mice. Cell. 2007 Jan 12;128(1):71-83. " Read Abstract.
  • Tu X, Joeng KS, Nakayama KI, Nakayama K, Rajagopal J, Carroll TJ, McMahon AP, Long F. Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell. 2007 Jan;12(1):113-27. Read Abstract.

Tissue Engineering

  • Weinand C, Gupta R, Huang AY, Weinberg E, Madisch I, Qudsi RA, Neville CM, Pomerantseva I, Vacanti JP. Comparison of Hydrogels in the In Vivo Formation of Tissue-Engineered Bone Using Mesenchymal Stem Cells and Beta-Tricalcium Phosphate. Tissue Eng. 2007 Jan 1; Read Abstract.

Translational Medicine

  • Adams GB, Martin RP, Alley IR, Chabner KT, Cohen KS, Calvi LM, Kronenberg HM, Scadden DT. Therapeutic targeting of a stem cell niche. Nat Biotechnol. 2007 Jan 21; Read Abstract.