Harvard Stem Cell Institute Research Newsletter
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| |  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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In an article paper published in The Journal of Experimental Medicine, HSCI Faculty Executive Committee member Diane Mathis, and HSCI Affiliated Faculty member Christophe Benoist, both of the Joslin Diabetes Center, report findings regarding the lineage relationship between conventional and regulatory T cells.
| | TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets Regulatory T cells are critical controllers of immune responses against self-proteins (autoimmunity), allergens, microbes and tumors. The best-characterized class, affectionately called Tregs, is marked by expression of the transcription factor, FoxP3. Current thinking holds that there are two types of FoxP3+ regulatory T cells: those produced constitutively in the thymus, termed natural Tregs, and those generated de novo during certain immune responses through conversion of the T cells actually engaged in the response, called T conventional cells. The lineage relationship between these two types of Tregs, and between them and T conventional cells is not known. This paper from the Benoist and Mathis lab uses the sequence of the antigen-specific receptor every T cell displays (T cell receptor or TCR) as a lineage tag to address to what extent T conventional cells convert to Tregs during an autoimmune response to a diabetogenic autoantigen expressed by pancreatic islet beta cells. Using single-cell sequencing of sorted Treg and T conventional cells from the pancreas and various lymphoid organs, they found no evidence of the latter converting into the former. It is important to understand just how Tregs can be generated, particularly during an autoimmune response, because of the current interest in infusing them for therapeutic purposes. Wong J, Mathis D, Benoist C. TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med. 2007 Sep 3;204(9):2039-45. Read abstract. | Review and Commentary Articles - Rosenzweig A. Scanning the genome for coronary risk. N Engl J Med. 2007 Aug 2;357(5):497-9. No abstract available. Read abstract.
- Jaffer FA, Libby P, Weissleder R. Molecular imaging of cardiovascular disease. Circulation. 2007 Aug 28;116(9):1052-61. Read abstract.
- Kim CF. Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells. Am J Physiol Lung Cell Mol Physiol. 2007 Aug 10. Read abstract.
- Park IH, Daley GQ. Debugging cellular reprogramming. Nat Cell Biol. 2007 Aug;9(8):871-3. Read abstract.
| Blood Disease - Feinberg MW, Wara AK, Cao Z, Lebedeva MA, Rosenbauer F, Iwasaki H, Hirai H, Katz JP, Haspel RL, Gray S, Akashi K, Segre J, Kaestner KH, Tenen DG, Jain MK. The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO J. 2007 Aug 30. Read abstract.
- Koschmieder S, D'Alo F, Radomska H, Schoneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Muller-Tidow C, Serve H, Tenen DG. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational upregulation of p42 CCAAT enhancer binding protein alpha. Blood. 2007 Aug 1. Read abstract.
- Saleque S, Kim J, Rooke HM, Orkin SH. Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1. Mol Cell. 2007 Aug 17;27(4):562-72. Read abstract.
- Geletu M, Balkhi MY, Peer Zada AA, Christopeit M, Pulikkan JA, Trivedi AK, Tenen DG, Behre G. Target proteins of C/EBP{alpha}-p30 in AML: C/EBP{alpha}-p30 enhances Sumoylation of C/EBP{alpha}-p42 via up regulation of Ubc9. Blood. 2007 Aug 10. Read abstract.
- Yeamans C, Wang D, Paz-Priel I, Torbett BE, Tenen DG, Friedman AD. C/EBP{alpha} binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood. 2007 Aug 1. Read abstract.
- Wouters BJ, Alberich Jorda M, Keeshan K, Louwers I, Erpelinck-Verschueren CA, Tielemans D, Langerak AW, He Y, Yashiro-Ohtani Y, Zhang P, Hetherington CJ, Verhaak RG, Valk PJ, Lowenberg B, Tenen DG, Pear WS, Delwel R. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood. 2007 Aug 1. Read abstract.
| Cancer - Nardi V, Raz T, Cao X, Wu CJ, Stone RM, Cortes J, Deininger MW, Church G, Zhu J, Daley GQ. Quantitative monitoring by polymerase colony assay of known mutations resistant to ABL kinase inhibitors. Oncogene. 2007 Aug 6. Read abstract.
- Gee MS, Upadhyay R, Bergquist H, Weissleder R, Josephson L, Mahmood U. Multiparameter noninvasive assessment of treatment susceptibility, drug target inhibition and tumor response guides cancer treatment. Int J Cancer. 2007 Aug 7. Read abstract.
| Development - Choi WY, Giraldez AJ, Schier AF. Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430. Science. 2007 Aug 30. Read abstract.
- Bahary N, Goishi K, Stuckenholz C, Weber G, Leblanc J, Schafer CA, Berman SS, Klagsbrun M, Zon LI. Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish. Blood. 2007 Aug 14. Read abstract.
- Abzhanov A, Rodda SJ, McMahon AP, Tabin CJ. Regulation of skeletogenic differentiation in cranial dermal bone. Development. 2007 Sep;134(17):3133-44. Read abstract.
| Diabetes - Koulmanda M, Budo E, Bonner-Weir S, Qipo A, Putheti P, Degauque N, Shi H, Fan Z, Flier JS, Auchincloss H Jr, Zheng XX, Strom TB. Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts. Proc Natl Acad Sci USA. 2007 Aug 7;104(32):13074-9. Read abstract.
- Wong J, Mathis D, Benoist C. TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med. 2007 Sep 3;204(9):2039-45. Read abstract.
| Genetics and Genomics - Hill AD, Chang BS, Hill RS, Garraway LA, Bodell A, Sellers WR, Walsh CA. A 2-Mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome. Am J Med Genet A. 2007 Aug 1;143(15):1692-8. Read abstract.
| Imaging - Kozloff KM, Weissleder R, Mahmood U. Noninvasive optical detection of bone mineral. J Bone Miner Res. 2007 Aug;22(8):1208-16. Read abstract.
- Arwert E, Hingtgen S, Figueiredo JL, Bergquist H, Mahmood U, Weissleder R, Shah K. Visualizing the dynamics of EGFR activity and antiglioma therapies in vivo. Cancer Res. 2007 Aug 1;67(15):7335-42. Read abstract.
| Immunology - Monach PA, Verschoor A, Jacobs JP, Carroll MC, Wagers AJ, Benoist C, Mathis D. Circulating C3 is necessary and sufficient for induction of autoantibody-mediated arthritis in a mouse model. Arthritis Rheum. 2007 Aug 30;56(9):2968-2974. Read abstract.
| Kidney Disease - Hentschel DM, Mengel M, Boehme L, Liebsch F, Albertin C, Bonventre JV, Haller H, Schiffer M. Rapid screening of glomerular slit diaphragm integrity in larval zebrafish. Am J Physiol Renal Physiol. 2007 Aug 15. Read abstract.
- Prozialeck WC, Vaidya VS, Liu J, Waalkes MP, Edwards JR, Lamar PC, Bernard AM, Dumont X, Bonventre JV. Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. Kidney Int. 2007 Aug 8. Read abstract.
- Chen G, Bridenbaugh EA, Akintola AD, Catania JM, Vaidya VS, Bonventre JV, Dearman AC, Sampson HW, Zawieja DC, Burghardt RC, Parrish AR. Increased Susceptibility of Aging Kidney to Ischemic Injury: Identification of Candidate Genes Changed During Aging, but Corrected by Caloric Restriction. Am J Physiol Renal Physiol. 2007 Aug 1. Read abstract.
| Nervous System Diseases - Hemming ML, Patterson M, Reske-Nielsen C, Lin L, Isacson O, Selkoe DJ. Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degradingprotease: a novel therapeutic approach to Alzheimer disease. PLoS Med. 2007 Aug 28;4(8):e262. Read abstract.
- Inoue H, Lin L, Lee X, Shao Z, Mendes S, Snodgrass-Belt P, Sweigard H, Engber T, Pepinsky B, Yang L, Beal MF, Mi S, Isacson O. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Natl Acad Sci USA. 2007 Sep 4;104(36):14430-5. Read abstract.
- Chung CY, Koprich JB, Endo S, Isacson O. An endogenous serine/threonine protein phosphatase inhibitor, G-substrate, reduces vulnerability in models of Parkinson's disease. J Neurosci. 2007 Aug 1;27(31):8314-23. Read abstract.
- Zappaterra MD, Lisgo SN, Lindsay S, Gygi SP, Walsh CA, Ballif BA. A Comparative Proteomic Analysis of Human and Rat Embryonic Cerebrospinal Fluid. J Proteome Res. 2007 Sep 7;6(9):3537-3548. Read abstract.
| Skeletal System - Xu L, Peng H, Glasson S, Lee PL, Hu K, Ijiri K, Olsen BR, Goldring MB, Li Y. Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007 Aug;56(8):2663-73. Read abstract.
| Technology - Shtatland T, Guettler D, Kossodo M, Pivovarov M, Weissleder R. PepBank - a database of peptides based on sequence text mining and public peptide data sources. BMC Bioinformatics. 2007 Aug 1;8(1):280. Read abstract.
- Link KH, Guo L, Ames TD, Yen L, Mulligan RC, Breaker RR. Engineering high-speed allosteric hammerhead ribozymes. Biol Chem. 2007 Aug;388(8):779-86. Read abstract.
| Tissue Engineering - Borenstein JT, Weinberg EJ, Orrick BK, Sundback C, Kaazempur-Mofrad MR, Vacanti JP. Microfabrication of three-dimensional engineered scaffolds. Tissue Eng. 2007 Aug;13(8):1837-44. Read abstract.
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