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Research Newsletter - March 2007

Spotlight

In a research paper published in Stem Cells, HSCI Principal Faculty Member, Patricia K. Donahoe and collaborators at the Harvard Stem Cell Institute and Massachusetts General Hospital, describe research that suggests that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Mullerian duct mesenchyme.

Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation

Conditional deletion of beta-catenin in the Mullerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in beta-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with BrdU and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs co-localized with alpha-smooth muscle actin, estrogen receptor-alpha, and beta-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing "side population" that expresses MISRII-Cre driven YFP. Functional response of LRCs was investigated by hCG stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Mullerian duct mesenchyme.

Szotek PP, Chang HL, Zhang L, Preffer F, Dombkowski D, Donahoe PK, Teixeira J. Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation. Stem Cells. 2007 Feb 8; Read Abstract.

Scientific Papers

Review and Commentary

  • "Kesari S, Jackson-Grusby L, Stiles CD. ""Smad""eningly erratic: target gene methylation determines whether TGFbeta promotes or suppresses malignant glioma. Dev Cell. 2007 Mar;12(3):324-5. " Read Abstract.
  • Humphreys BD, Bonventre JV. The contribution of adult stem cells to renal repair. Nephrol Ther. 2007 Mar;3(1):3-10. Epub 2007 Feb 22. Read Abstract.
  • Reginato AM, Olsen BR. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear? Curr Opin Rheumatol. 2007 Mar;19(2):134-45. Review. Read Abstract.

Blood

  • Babic AM, Josefsson EC, Bergmeier W, Wagner DD, Kaufman RM, Silberstein LE, Stossel TP, Hartwig JH, Hoffmeister KM. In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration. Transfusion. 2007 Mar;47(3):442-51. Read Abstract.
  • Chen Z, Naveiras O, Balduini AA, Mammoto A, Conti MA, Adelstein RS, Ingber D, Daley GQ, Shivdasani RA. The May-Hegglin anomaly gene Myh9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. Blood. 2007 Mar 28; Read Abstract.
  • Gu TL, Mercher T, Tyner JW, Goss VL, Walters DK, Cornejo MG, Reeves C, Popova L, Lee K, Rush J, Daibata M, Miyoshi I, Gilliland DG, Druker BJ, Polakiewicz RD. A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia. Blood. 2007 Mar 14; Read Abstract.
  • Kikawada E, Bonventre JV, Arm JP. Group V secretory PLA2 regulates TLR2-dependent eicosanoid generation in mouse mast cells through amplification of ERK and cPLA2{alpha} activation. Blood. 2007 Mar 16; Read Abstract.
  • Raffel GD, Mercher T, Shigematsu H, Williams IR, Cullen DE, Akashi K, Bernard OA, Gilliland DG. Ott1(Rbm15) has pleiotropic roles in hematopoietic development. Proc Natl Acad Sci USA. 2007 Apr 3;104(14):6001-6. Epub 2007 Mar 21. Read Abstract.

Cancer

  • Butler MO, Lee JS, Ansen S, Neuberg D, Hodi FS, Murray AP, Drury L, Berezovskaya A, Mulligan RC, Nadler LM, Hirano N. Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Clin Cancer Res. 2007 Mar 15;13(6):1857-67. Read Abstract.
  • Gupta V, Yeo G, Kawakubo H, Rangnekar V, Ramaswamy P, Hayashida T, MacLaughlin DT, Donahoe PK, Maheswaran S. Mullerian-inhibiting substance induces Gro-beta expression in breast cancer cells through a nuclear factor-kappaB-dependent and Smad1-dependent mechanism. Cancer Res. 2007 Mar 15;67(6):2747-56. Read Abstract.
  • Lin F, Zhang PL, Yang XJ, Shi J, Blasick T, Han WK, Wang HL, Shen SS, Teh BT, Bonventre JV. Human Kidney Injury Molecule-1 (hKIM-1): A Useful Immunohistochemical Marker for Diagnosing Renal Cell Carcinoma and Ovarian Clear Cell Carcinoma. Am J Surg Pathol. 2007 Mar;31(3):371-381. Read Abstract.
  • Scholl C, Bansal D, Dohner K, Eiwen K, Huntly BJ, Lee BH, Rucker FG, Schlenk RF, Bullinger L, Dohner H, Gilliland DG, Frohling S. The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. J Clin Invest. 2007 Apr 2;117(4):1037-1048. Epub 2007 Mar 8. Read Abstract.
  • Tefferi A, Gilliland DG. Oncogenes in myeloproliferative disorders. Cell Cycle. 2007 Mar;6(5):550-66. Epub 2007 Mar 24. Read Abstract.

Cardiovascular System

  • Duhaney TA, Cui L, Rude MK, Lebrasseur NK, Ngoy S, De Silva DS, Siwik DA, Liao R, Sam F. Peroxisome Proliferator-Activated Receptor {alpha}-Independent Actions of Fenofibrate Exacerbates Left Ventricular Dilation and Fibrosis in Chronic Pressure Overload. Hypertension. 2007 Mar 12; Read Abstract.
  • Pomies P, Pashmforoush M, Vegezzi C, Chien KR, Auffray C, Beckerle MC. The Cytoskeleton-associated PDZ-LIM Protein, ALP, Acts on SRF Activity to Regulate Muscle Differentiation. Mol Biol Cell. 2007 Mar 1; Read Abstract.
  • Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME, Harvey RP. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell. 2007 Mar 9;128(5):947-59. Read Abstract.
  • Sosnovik DE, Nahrendorf M, Deliolanis N, Novikov M, Aikawa E, Josephson L, Rosenzweig A, Weissleder R, Ntziachristos V. Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation. 2007 Mar 20;115(11):1384-91. Epub 2007 Mar 5. Read Abstract.
  • Teutsch C, Kondo RP, Dederko DA, Chrast J, Chien KR, Giles WR. Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection. Cardiovasc Res. 2007 Mar 1;73(4):739-49. Epub 2006 Nov 30. Read Abstract.

Developmental Biology

  • Lengerke C, Kim K, Lerou P, Daley GQ. Differentiation potential of histocompatible parthenogenetic embryonic stem cells. Ann N Y Acad Sci. 2007 Mar 14; Read Abstract.
  • Liston A, Farr AG, Chen Z, Benoist C, Mathis D, Manley NR, Rudensky AY. Lack of Foxp3 function and expression in the thymic epithelium. J Exp Med. 2007 Mar 19;204(3):475-80. Epub 2007 Mar 12. Read Abstract.
  • Steffen LS, Guyon JR, Vogel ED, Beltre R, Pusack TJ, Zhou Y, Zon LI, Kunkel LM. Zebrafish orthologs of human muscular dystrophy genes. BMC Genomics. 2007 Mar 20;8(1):79 Read Abstract.

Diabetes

  • Arikawa E, Ma RC, Isshiki K, Luptak I, He Z, Yasuda Y, Maeno Y, Elizabeth Patti M, Weir GC, Harris RA, Zammit VA, Tian R, King GL. Effects of Insulin Replacements, Inhibitors of Angiotensin and Protein Kinase C{beta}'s Actions to Normalize Cardiac Gene Expression and Fuel Metabolism in Diabetic Rats. Diabetes. 2007 Mar 15; Read Abstract.
  • Papas KK, Colton CK, Nelson RA, Rozak PR, Avgoustiniatos ES, Scott WE 3rd, Wildey GM, Pisania A, Weir GC, Hering BJ. Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice. Am J Transplant. 2007 Mar;7(3):707-13. Epub 2007 Jan 4. Read Abstract.
  • Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, King GL, Weir GC, Bonner-Weir S. Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia: Possible Contribution to Impaired Incretin Effects in Diabetes. Diabetes. 2007 Mar 14; Read Abstract.
  • Yatoh S, Akashi T, Chan PP, Kaneto H, Sharma A, Bonner-Weir S, Weir GC. NeuroD and reaggregation induce beta-cell specific gene expression in cultured hepatocytes. Diabetes Metab Res Rev. 2007 Mar;23(3):239-49. Read Abstract.

Imaging

  • Ho NH, Weissleder R, Tung CH. A Self-Immolative Reporter For beta-Galactosidase Sensing. Chembiochem. 2007 Mar 26;8(5):560-566. Weissleder R. Dual Channel Optical Tomographic Imaging of Leukocyte Recruitment and Protease Activity in the Healing Myocardial Infarct. Circ Res. 2007 Mar 22; Read Abstract.
  • Montet X, Figueiredo JL, Alencar H, Ntziachristos V, Mahmood U, Weissleder R. Tomographic fluorescence imaging of tumor vascular volume in mice. Radiology. 2007 Mar;242(3):751-8. Read Abstract.
  • Yuan H, Barnes KR, Weissleder R, Cantley L, Josephson L. Covalent Reactions of Wortmannin under Physiological Conditions. Chem Biol. 2007 Mar;14(3):321-8. Read Abstract.

Immunology

  • Gavanescu I, Kessler B, Ploegh H, Benoist C, Mathis D. Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc Natl Acad Sci USA. 2007 Mar 13;104(11):4583-7. Epub 2007 Mar 6. Read Abstract.

Nervous System

  • Peng CY, Yajima H, Burns CE, Zon LI, Sisodia SS, Pfaff SL, Sharma K. Notch and MAML Signaling Drives Scl-Dependent Interneuron Diversity in the Spinal Cord. Neuron. 2007 Mar 15;53(6):813-27. Read Abstract.
  • Zhang J, Vinuela A, Neely MH, Hallett PJ, Grant SG, Miller GM, Isacson O, Caron MG, Yao WD. Inhibition of the dopamine D1 receptor signaling by PSD-95. J Biol Chem. 2007 Mar 16; Read Abstract.

Translational Medicine

  • Peault B, Rudnicki M, Torrente Y, Cossu G, Tremblay JP, Partridge T, Gussoni E, Kunkel LM, Huard J. Stem and Progenitor Cells in Skeletal Muscle Development, Maintenance, and Therapy. Mol Ther. 2007 Mar 27; Read Abstract.