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


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.

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Spotlight

In a review article paper published in Néphrologie & Thérapeutique, HSCI Principal Faculty Member, Joseph V. Bonventre and Affiliated Faculty Member, Benjamin D. Humphreys survey the role of adult stem cells in renal repair.
The contribution of adult stem cells to renal repair

The kidney undergoes continuous, slow cellular turnover for tissue maintenance and rapid cell replacement after injury. The cellular origin of newly differentiated tubular epithelium remains controversial. In some non-renal organs, adult stem cells are recognized as the cell of origin for tissue replacement, such as the hematopoietic system, intestine and skin. These findings have prompted intense investigation for evidence of renal stem cells because of the great need for new therapeutic approaches to treat acute kidney injury and chronic kidney disease. Early excitement at reports that bone marrow-derived cells transdifferentiate into renal epithelial cells has been tempered by findings that show such events to be rare or potentially explained by cell fusion. More recent studies have focused on the possibility that renal progenitors exist within the kidney. In this review we compare data supporting the existence of adult renal stem cells with the body of evidence indicating that the kidney regenerates by self-duplication of differentiated cells. The identification of adult renal epithelial progenitor cells will ultimately determine the future direction of renal regenerative medicine.


Figure 1. The origin of epithelial progenitors in acute kidney injury.After an ischemic renal injury, tubular epithelia undergo both apoptosis and necrosis, with decreased cell-cell contacts and sloughing of dead cells into the tubular lumen. Repopulation of the denuded basement membrane may occur by dedifferentiation of surviving epithelial cells with subsequent proliferation of any cells that survive the original injury (A). Alternatively, there may be a subset of intra-tubular stem cells (B) that are resistant to injury, and selectively respond to injury by proliferating. Finally, regeneration may be accomplished by migration of extra-tubular stem cells (e.g. bone marrow-derived or renal papilla resident stem cells) that cross the basement membrane into the tubule. Once within they tubule, they may contribute to renal regeneration either by fusion with surviving, dedifferentiated epithelial cells or by subsequent proliferation and differentiation into mature renal epithelium (C).





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 Article.
Review and Commentary Articles
  • 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.
  • 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.
Scientific Papers
Blood Disease
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Cancer
  • 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.
  • 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.
  • 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.
  • 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 Disease
  • 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.
  • 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.
  • 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.
  • 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.
Development
  • 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.
  • 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.
  • 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.
Diabetes 
  • 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.
  • 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.
  • 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.
Imaging
  • 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.
  • Ho NH, Weissleder R, Tung CH. A Self-Immolative Reporter For beta-Galactosidase Sensing. Chembiochem. 2007 Mar 26;8(5):560-566. Read Abstract.
  • Nahrendorf M, Sosnovik DE, Waterman P, Swirski FK, Pande A, Aikawa E, Figueiredo JL, Pittet MJ, 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.
  • 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 Diseases 
  • 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.

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