Harvard Stem Cell Institute Research Newsletter
SPOTLIGHT
REVIEW and COMMENTARY ARTICLES
SCIENTIFIC PAPERS
blood disease
cancer
cardiovascular disease
development
imaging
immunology
nervous system diseases
technology


This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month. To continue receiving this newsletter, please register as an HSCI Affiliate or Friend by clicking here.

If you are having problems viewing this newletter, click here to view it in your web browser.

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.



Supplemental Figure 1.  Model of myometrial cell progenitors.  Myometrial cells can be classified into several populations by immunofluorescence and flow cytometry.  BrdU label retaining cells (LRCs) might be the most primitive cells or stem cells that divide to regenerate themselves and daughter progenitor cells that are BrdUdim and c-kit+.  We also observed that MISRII-Cre driven YFP expressing cells were enriched in the SP and could differentiate into αSMA-expressing cells in culture suggesting that more committed progenitor cell than the BrdUdim/c-kit+ cell.  In this model, these populations represent various stages of differentiation into smooth muscle cells.







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.
Review and Commentary Articles
  • Rosenbauer F, Tenen DG. Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol. 2007 Feb;7(2):105-17. Read Abstract.
  • Daley GQ, Richter LA, Auerbach JM, Benvenisty N, Charo RA, Chen G, Deng HK, Goldstein LS, Hudson KL, Hyun I, Junn SC, Love J, Lee EH, McLaren A, Mummery CL, Nakatsuji N, Racowsky C, Rooke H, Rossant J, Scholer HR, Solbakk JH, Taylor P, Trounson AO, Weissman IL, Wilmut I, Yu J, Zoloth L. Ethics. The ISSCR guidelines for human embryonic stem cell research. Science. 2007 Feb 2;315(5812):603-4. No abstract available. Read Abstract.
  • Hochedlinger K, Jaenisch R. On the cloning of animals from terminally differentiated cells. Nat Genet. 2007 Feb;39(2):136-7. No abstract available. Read Abstract.
  • Vacanti JP. Editorial: tissue engineering: a 20-year personal perspective. Tissue Eng. 2007 Feb;13(2):231-2. No abstract available. Read Abstract.
  • Wang Y, McMahon AP, Allen BL. Shifting paradigms in Hedgehog signaling. Curr Opin Cell Biol. 2007 Feb 13; Read Abstract.
Scientific Papers
Blood Disease
  • Zhang J, Scadden DT, Crumpacker CS. Primitive hematopoietic cells resist HIV-1 infection via p21. J Clin Invest. 2007 Feb 1;117(2):473-481. Read Abstract.
  • Koschmieder S, Agrawal S, Radomska HS, Huettner CS, Tenen DG, Ottmann OG, Berdel WE, Serve HL, Muller-Tidow C. Decitabine and vitamin D3 differentially affect hematopoietic transcription factors to induce monocytic differentiation. Int J Oncol. 2007 Feb;30(2):349-55. Read Abstract.
  • Liu TX, Rhodes J, Deng M, Hsu K, Radomska HS, Kanki JP, Tenen DG, Look AT. Dominant-interfering C/EBPalpha stimulates primitive erythropoiesis in zebrafish. Exp Hematol. 2007 Feb;35(2):230-9. Read Abstract.
  • Lengerke C, McKinney-Freeman S, Naveiras O, Yates F, Wang Y, Bansal D, Daley GQ. The Cdx-Hox pathway in hematopoietic stem cell formation from embryonic stem cells. Ann N Y Acad Sci. 2007 Feb 15; Read Abstract.
Cancer
  • Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, Futreal PA, Erber WN, McMullin MF, Harrison CN, Warren AJ, Gilliland DG, Lodish HF, Green AR. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007 Feb 1;356(5):459-68. Read Abstract.
  • Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, Macconnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R, Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 2007 Mar;39(3):347-351. Epub 2007 Feb 11. Read Abstract.
Cardiovascular Disease
  • Wang ZZ, Au P, Chen T, Shao Y, Daheron LM, Bai H, Arzigian M, Fukumura D, Jain RK, Scadden DT. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol. 2007 Feb 25; Read Abstract.
  • Leopold JA, Dam A, Maron BA, Scribner AW, Liao R, Handy DE, Stanton RC, Pitt B, Loscalzo J. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med. 2007 Mar;13(2):189-197. Epub 2007 Feb 4. Read Abstract.
Development
  • 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.
  • Klose RJ, Yan Q, Tothova Z, Yamane K, Erdjument-Bromage H, Tempst P, Gilliland DG, Zhang Y, Kaelin WG Jr. The Retinoblastoma Binding Protein RBP2 Is an H3K4 Demethylase. Cell. 2007 Feb 21; Read Abstract.
  • Ghosh M, Loper R, Ghomashchi F, Tucker DE, Bonventre JV, Gelb MH, Leslie CC. Function, activity and membrane targeting of cytosolic phospholipase A2zeta in mouse lung fibroblasts. J Biol Chem. 2007 Feb 11; Read Abstract.
  • Grondin B, Lefrancois M, Tremblay M, Saint-Denis M, Haman A, Waga K, Bedard A, Tenen DG, Hoang T. c-Jun homodimers can function as a context-specific coactivator. Mol Cell Biol. 2007 Feb 5; Read Abstract.
Imaging
  • Nahrendorf M, Badea C, Hedlund LW, Figueiredo JL, Sosnovik DE, Johnson GA, Weissleder R. High Resolution Imaging of Murine Myocardial Infarction With Delayed Enhancement Cine Micro-CT. Am J Physiol Heart Circ Physiol. 2007 Feb 23; Read Abstract.
  • Ho NH, Weissleder R, Tung CH. A Self-Immolative Reporter For beta-Galactosidase Sensing. Chembiochem. 2007 Feb 15; Read Abstract.
Immunology
  • Hill JA, Benoist C, Mathis D. T(reg) cells: guardians for life. Nat Immunol. 2007 Feb;8(2):124-125. No abstract available. Read Abstract.
  • Nigrovic PA, Binstadt BA, Monach PA, Johnsen A, Gurish M, Iwakura Y, Benoist C, Mathis D, Lee DM. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2325-30. Read Abstract.
  • Haxhinasto S, Benoist C, Mathis D. Regulatory T-cell differentiation: Committed to control: a precocious choice? Immunol Cell Biol. 2007 Feb 20; No abstract available. Read Abstract.
  • Bihl F, Narayan M, Chisholm JV 3rd, Henry LM, Suscovich TJ, Brown EE, Welzel TM, Kaufmann DE, Zaman TM, Dollard S, Martin JN, Wang F, Scadden DT, Kaye KM, Brander C. Lytic and latent antigens of the human {gamma}-herpesviruses KSHV and EBV induce T cell responses with similar functional properties and memory phenotypes. J Virol. 2007 Feb 28; Read Abstract.
  • Nguyen LT, Jacobs J, Mathis D, Benoist C. Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum. 2007 Feb;56(2):509-20. Read Abstract.
 
Nervous System Diseases 
  • Seo H, Sonntag KC, Kim W, Cattaneo E, Isacson O. Proteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cells. PLoS ONE. 2007 Feb 28;2:e238. Read Abstract.
Technology 
  • Galante PA, Trimarchi J, Cepko CL, de Souza SJ, Ohno-Machado L, Kuo WP. Automatic Correspondence of Tags and Genes (ACTG): A Tool for the Analysis of SAGE, MPSS, and SBS Data. Bioinformatics. 2007 Feb 3; Read Abstract.

The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions.

Visit our website at www.hsci.harvard.edu

If there is anything that you would like to see added to this email alert, please email maureen_lyons@harvard.edu.
Photo courtesy of B.D.Colen.
Copyright © 2007 President and Fellows of Harvard College. All rights reserved.