Home » Newsroom » Research Newsletter » Research Newsletter - August 2007

Research Newsletter - August 2007

Spotlight

In an article paper published in Developmental Cell, HSCI Scientific Co-Director, Douglas Melton and collaborators at the Department of Molecular and Cellular Biology, Harvard University, report findings that define a multipotent compartment within the developing pancreas and suggest a model of how branching is coordinated with cell type specification.

A Multipotent Progenitor Domain Guides Pancreatic Organogenesis

The mammalian pancreas is constructed during embryogenesis by multipotent progenitors, the identity and function of which remain poorly understood. We performed genome-wide transcription factor expression analysis of the developing pancreas to identify gene expression domains that may represent distinct progenitor cell populations. Five discrete domains were discovered. Genetic lineage-tracing experiments demonstrate that one specific domain, located at the tip of the branching pancreatic tree, contains multipotent progenitors that produce exocrine, endocrine, and duct cells in vivo. These multipotent progenitors are Pdx1+Ptf1a+cMycHighCpa1+ and negative for differentiated lineage markers. The outgrowth of multipotent tip cells leaves behind differentiated progeny that form the trunk of the branches. These findings define a multipotent compartment within the developing pancreas and suggest a model of how branching is coordinated with cell type specification. In addition, this comprehensive analysis of >1,100 transcription factors identified genes that are likely to control critical decisions in pancreas development and disease.

Zhou Q, Law AC, Rajagopal J, Anderson WJ, Gray PA, Melton DA. A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell. 2007 Jul;13(1):103-14. Read Abstract.
 

Scientific Papers

Review and Commentary

  • Eggan K. Short-circuiting epiblast development. Cell Stem Cell. 2007 Aug 16;1(2):131-2. 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.
  • Lo Celso C, Scadden DT. Stem cells remember their grade. Cell Stem Cell. 2007 Aug 16;1(2):132-4. Read Abstract.
  • Park IH, Daley GQ. Debugging cellular reprogramming. Nat Cell Biol. 2007 Aug;9(8):871-3. Read Abstract.
  • Rosenzweig A. Scanning the genome for coronary risk. N Engl J Med. 2007 Aug 2;357(5):497-9. No abstract available. Read Abstract.
  • Tothova Z, Gilliland DG. FoxO transcription factors and stem cell homeostasis: insights from the hematopoietic system. Cell Stem Cell. 2007 Aug 16;1(2):140-52. Read Abstract.

Blood

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Cancer

  • 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.
  • 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.

Cardiovascular System

  • Qyang Y, Martin-Puig S, Chiravuri M, Chen S, Xu H, Bu L, Jiang X, Lin L, Granger A, Moretti A, Caron L, Wu X, Clarke J, Taketo MM, Laugwitz KL, Moon RT, Gruber P, Evans SM, Ding S, Chien KR. The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway. Cell Stem Cell. 2007 Aug 16;1(2):165-79. Epub 2007 Jun 14. Read Abstract.

Developmental Biology

  • 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.
  • 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.
  • 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.

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

  • 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.
  • Kozloff KM, Weissleder R, Mahmood U. Noninvasive optical detection of bone mineral. J Bone Miner Res. 2007 Aug;22(8):1208-16. 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.

Nervous System

  • 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.
  • 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.
  • 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.

Renal System

  • 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.
  • 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.

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

  • 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.
  • 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.

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.