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Research Newsletter - April 2008

Spotlight

This month's spotlighted article is by Affiliated Faculty member Benjamin D. Humphreys, MD, PhD, Principal Faculty member Joseph V. Bonventre, MD, PhD of Brigham and Women's Hospital, and HSCI Executive Committee member Andrew McMahon, PhD of Harvard University.

Intrinsic epithelial cells repair the kidney after injury

Abstract:

Understanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%-95% of tubular epithelial cells, but no interstitial cells, were labeled with either beta-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney.

Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008 Mar 6;2(3):284-91. Read Paper.

Scientific Papers

Review and Commentary

  • de Koning EJ, Bonner-Weir S, Rabelink TJ. Preservation of beta-cell function by targeting beta-cell mass. Trends Pharmacol Sci. 2008 Mar 20. Read Abstract.
  • Ferguson MA, Vaidya VS, Bonventre JV. Biomarkers of nephrotoxic acute kidney injury. Toxicology. 2008 Mar 20;245(3):182-93. Epub 2008 Jan 4. Read Abstract.
  • Karra R, Wu SM. Multipotent stem cells in cardiac regenerative therapy. Regen Med. 2008 Mar;3(2):189-98. Read Abstract.
  • Kreidberg JA. Integrins and matrix in the glomerulus: old mysteries and new insights. J Am Soc Nephrol. 2008 Apr;19(4):650-1. Epub 2008 Mar 5. Read Abstract.
  • Li Q, Gregory RI. MicroRNA Regulation of Stem Cell Fate. Cell Stem Cell. 2008 Mar 6;2(3):195-6. Read Abstract.
  • Lock EA, Bonventre JV. Biomarkers in translation; past, present and future. Toxicology. 2008 Mar 20;245(3):163-6. Epub 2007 Dec 17. Read Abstract.
  • Scadden DT. Circadian rhythms: stem cells traffic in time. Nature. 2008 Mar 27;452(7186):416-7. Read Abstract.
  • Williams DA. NIH recombinant DNA Advisory Committee continues to ponder adverse event associated with AAV gene therapy trial. Mol Ther. 2008 Mar;16(3):427-8. Read Abstract.
  • Wingert RA, Davidson AJ. The zebrafish pronephros: A model to study nephron segmentation. Kidney Int. 2008 Mar 5. Read Abstract.

Blood

  • Austin KM, Gupta ML, Coats SA, Tulpule A, Mostoslavsky G, Balazs AB, Mulligan RC, Daley G, Pellman D, Shimamura A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest. 2008 Mar 6. Read Abstract.
  • Chae HD, Lee KE, Williams DA, Gu Y. Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells. Blood. 2008 Mar 1;111(5):2597-605. Epub 2007 Dec 18. Read Abstract.
  • Fleming HE, Janzen V, Lo Celso C, Guo J, Leahy KM, Kronenberg HM, Scadden DT. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008 Mar 6;2(3):274-83. Read Abstract.
  • Jia Y, Loison F, Hattori H, Li Y, Erneux C, Park SY, Gao C, Chai L, Silberstein LE, Schurmans S, Luo HR. Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci USA. 2008 Mar 25;105(12):4739-44. Epub 2008 Mar 13. Read Abstract.
  • Pardanani A, Fridley BL, Lasho TL, Gilliland DG, Tefferi A. Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood. 2008 Mar 1;111(5):2785-9. Epub 2007 Nov 15. Read Abstract.
  • Rhodes KE, Gekas C, Wang Y, Lux CT, Francis CS, Chan DN, Conway S, Orkin SH, Yoder MC, Mikkola HK. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell. 2008 Mar 6;2(3):252-63. Read Abstract.

Cancer

  • Costa DB, Schumer ST, Tenen DG, Kobayashi S. Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations. J Clin Oncol. 2008 Mar 1;26(7):1182-4; author reply 1184-6. No abstract available. Read Abstract.
  • Langenau DM, Keefe MD, Storer NY, Jette CA, Smith AC, Ceol CJ, Bourque C, Look AT, Zon LI. Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene. 2008 Mar 17. Read Abstract.
  • Lasho TL, Tefferi A, Hood JD, Verstovsek S, Gilliland DG, Pardanani A. TG101348, a JAK2-selective antagonist, inhibits primary hematopoietic cells derived from myeloproliferative disorder patients with JAK2V617F, MPLW515K or JAK2 exon 12 mutations as well as mutation negative patients. Leukemia. 2008 Mar 20. Read Abstract.
  • Swanson KD, Winter JM, Reis M, Bentires-Alj M, Greulich H, Grewal R, Hruban RH, Yeo CJ, Yassin Y, Iartchouk O, Montgomery K, Whitman SP, Caligiuri MA, Loh ML, Gilliland DG, Look AT, Kucherlapati R, Kern SE, Meyerson M, Neel BG. SOS1 mutations are rare in human malignancies: implications for Noonan Syndrome patients. Genes Chromosomes Cancer. 2008 Mar;47(3):253-9. Read Abstract.
  • Thomas EK, Cancelas JA, Zheng Y, Williams DA. Rac GTPases as key regulators of p210-BCR-ABL-dependent leukemogenesis. Leukemia. 2008 Mar 20. Read Abstract.

Cardiovascular System

  • Chan JY, Takeda M, Briggs LE, Graham ML, Lu JT, Horikoshi N, Weinberg EO, Aoki H, Sato N, Chien KR, Kasahara H. Identification of cardiac-specific myosin light chain kinase. Circ Res. 2008 Mar 14;102(5):571-80. Epub 2008 Jan 17. Read Abstract.
  • Kontaridis MI, Yang W, Bence KK, Cullen D, Wang B, Bodyak N, Ke Q, Hinek A, Kang PM, Liao R, Neel BG. Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways. Circulation. 2008 Mar 18;117(11):1423-35. Epub 2008 Mar 3. Read Abstract.

Developmental Biology

  • Kim J, Chu J, Shen X, Wang J, Orkin SH. An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 2008 Mar 21;132(6):1049-61. Read Abstract.
  • Narala SR, Allsopp RC, Wells TB, Zhang G, Prasad P, Coussens MJ, Rossi DJ, Weissman IL, Vaziri H. SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and Its Loss Is Associated with Increased AMPK and Telomerase Activity. Mol Biol Cell. 2008 Mar;19(3):1210-9. Epub 2008 Jan 9. Read Abstract.
  • Paulsen FP, Woon CW, Varoga D, Jansen A, Garreis F, J√¢ÀÜ≈°√Ǭßger K, Amm M, Podolsky DK, Steven P, Barker NP, Sel S. ITF/TFF3 promotes re-epithelialization of corneal wounds. J Biol Chem. 2008 Mar 7. Read Abstract.
  • Punzo C, Cepko CL. Ultrasound-guided in utero injections allow studies of the development and function of the eye. Dev Dyn. 2008 Mar 19;237(4):1034-1042 [Epub ahead of print] Read Abstract.
  • Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K, Brykczynska U, Kolb C, Otte AP, Koseki H, Orkin SH, van Lohuizen M, Peters AH. PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet. 2008 Apr;40(4):411-20. Epub 2008 Mar 2. Read Abstract.
  • Rajagopal J, Carroll TJ, Guseh JS, Bores SA, Blank LJ, Anderson WJ, Yu J, Zhou Q, McMahon AP, Melton DA. Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme. Development. 2008 Mar 26. Read Abstract.
  • Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining Molecular Cornerstones during Fibroblast to iPS Cell Reprogramming in Mouse. Cell Stem Cell. 2008 Mar 6;2(3):230-40. Epub 2008 Feb 14. Read Abstract.
  • Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 2008 Mar 21;132(6):1025-38. Read Abstract.

Diabetes

  • Marselli L, Thorne J, Ahn YB, Omer A, Sgroi DC, Libermann T, Otu HH, Sharma A, Bonner-Weir S, Weir GC. Gene Expression of Purified {beta}-Cell Tissue Obtained from Human Pancreas with Laser Capture Microdissection. J Clin Endocrinol Metab. 2008 Mar;93(3):1046-53. Epub 2007 Dec 11. Read Abstract.

Imaging

  • Figueiredo JL, Passerotti CC, Sponholtz T, Nguyen HT, Weissleder R. A novel method of imaging calcium urolithiasis using fluorescence. J Urol. 2008 Apr;179(4):1610-4. Epub 2008 Mar 4. Read Abstract.
  • Guimaraes AR, Tabatabei S, Dahl D, McDougal WS, Weissleder R, Harisinghani MG. Pilot Study Evaluating Use of Lymphotrophic Nanoparticle-Enhanced Magnetic Resonance Imaging for Assessing Lymph Nodes in Renal Cell Cancer. Urology. 2008 Mar 4. Read Abstract.
  • Hong R, Cima MJ, Weissleder R, Josephson L. Magnetic microparticle aggregation for viscosity determination by MR. Magn Reson Med. 2008 Mar;59(3):515-20. Read Abstract.
  • Nahrendorf M, Sosnovik DE, Weissleder R MR-optical imaging of cardiovascular molecular targets. Basic Res Cardiol. 2008 Mar;103(2):87-94. Read Abstract.
  • Sosnovik DE, Nahrendorf M, Weissleder R. Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications. Basic Res Cardiol. 2008 Mar;103(2):122-30. Read Abstract.

Immunology

  • Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ. Blood Monocyte Subsets Differentially Give Rise to CD103+ and CD103- Pulmonary Dendritic Cell Populations. J Immunol. 2008 Mar 1;180(5):3019-27. Read Abstract.

Pulmonary System

  • Demchenko IT, Atochin DN, Gutsaeva DR, Godfrey RR, Huang PL, Piantadosi CA, Allen BW. Contributions of Nitric Oxide Synthase Isoforms to Pulmonary Oxygen Toxicity, Local vs. Mediated Effects. Am J Physiol Lung Cell Mol Physiol. 2008 Mar 7. Read Abstract.

Renal System

  • Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008 Mar 6;2(3):284-91. Read Abstract.
  • Zhang PL, Rothblum LI, Han WK, Blasick TM, Potdar S, Bonventre JV. Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury. Kidney Int. 2008 Mar;73(5):608-14. Epub 2007 Dec 26. Read Abstract.

Technology

  • Deutsch EW, Ball CA, Berman JJ, Bova GS, Brazma A, Bumgarner RE, Campbell D, Causton HC, Christiansen JH, Daian F, Dauga D, Davidson DR, Gimenez G, Goo YA, Grimmond S, Henrich T, Herrmann BG, Johnson MH, Korb M, Mills JC, Oudes AJ, Parkinson HE, Pascal LE, Pollet N, Quackenbush J, Ramialison M, Ringwald M, Salgado D, Sansone SA, Sherlock G, Stoeckert CJ Jr, Swedlow J, Taylor RC, Walashek L, Warford A, Wilkinson DG, Zhou Y, Zon LI, Liu AY, True LD. Minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). Nat Biotechnol. 2008 Mar;26(3):305-12. Read Abstract.
  • Osafune K, Caron L, Borowiak M, Martinez RJ, Fitz-Gerald CS, Sato Y, Cowan CA, Chien KR, Melton DA. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol. 2008 Mar;26(3):313-5. Epub 2008 Feb 17. Read Abstract.
  • Shin M, Abukawa H, Troulis MJ, Vacanti JP. Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering. J Biomed Mater Res A. 2008 Mar 1;84(3):702-9. Read Abstract.