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Research Newsletter - April 2009

Spotlight

In an article paper published in Cell, HSCI Principal Faculty Members Wolfram Goessling, MD, PhD, Trista North, PhD, Georgy Daley, MD, PhD, Leonard Zon, MD, and colleagues report in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests that the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery.

Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration

Abstract:

Interactions between developmental signaling pathways govern the formation and function of stem cells. Prostaglandin (PG) E2 regulates vertebrate hematopoietic stem cells (HSC). Similarly, the Wnt signaling pathway controls HSC self-renewal and bone marrow repopulation. Here, we show that wnt reporter activity in zebrafish HSCs is responsive to PGE2 modulation, demonstrating a direct interaction in vivo. Inhibition of PGE2 synthesis blocked wnt-induced alterations in HSC formation. PGE2 modified the wnt signaling cascade at the level of beta-catenin degradation through cAMP/PKA-mediated stabilizing phosphorylation events. The PGE2/Wnt interaction regulated murine stem and progenitor populations in vitro in hematopoietic ES cell assays and in vivo following transplantation. The relationship between PGE2 and Wnt was also conserved during regeneration of other organ systems. Our work provides in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery.

Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009 Mar 20;136(6):1136-47. Read paper.

Scientific Papers

Review and Commentary

  • Daley GQ, Lensch MW, Jaenisch R, Meissner A, Plath K, Yamanaka S. Broader implications of defining standards for the pluripotency of iPSCs. Cell Stem Cell. 2009 Mar 6;4(3):200-1. Read Abstract.
  • Ebert BL. Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer. Leukemia. 2009 Mar 26. [Epub ahead of print] Read Abstract.
  • Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell. 2009 Mar 6;4(3):206-16. Read Abstract.
  • Muller LU, Daley GQ, Williams DA. Upping the Ante: Recent Advances in Direct Reprogramming. Mol Ther. 2009 Mar 31. [Epub ahead of print] Read Abstract.
  • Nathan DG, Orkin SH. Musings on genome medicine: the Obama effect. Genome Med. 2009 Mar 9;1(3):30. [Epub ahead of print] Read Abstract.
  • Neff T, Armstrong SA. Chromatin maps, histone modifications and leukemia. Leukemia. 2009 Mar 26. [Epub ahead of print] Read Abstract.
  • Tothova Z, Gilliland DG A radical bailout strategy for cancer stem cells. Cell Stem Cell. 2009 Mar 6;4(3):196-7. Read Abstract.
  • Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009 Mar;11(3):228-34. Review. Read Abstract.
  • Yusuf RZ, Scadden DT. Homing of hematopoietic cells to the bone marrow. J Vis Exp. 2009 Mar 18;(25). pii: 1104. doi: 10.3791/1104. Read Abstract.

Blood

  • Adams GB, Alley IR, Chung UI, Chabner KT, Jeanson NT, Celso CL, Marsters ES, Chen M, Weinstein LS, Lin CP, Kronenberg HM, Scadden DT. Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow. Nature. 2009 Mar 25. [Epub ahead of print] Read Abstract.
  • Burns CE, Galloway JL, Smith AC, Keefe MD, Cashman TJ, Paik EJ, Mayhall EA, Amsterdam AH, Zon LI. A genetic screen in zebrafish defines a hierarchical network of pathways required for hematopoietic stem cell emergence. Blood. 2009 Mar 30. [Epub ahead of print] Read Abstract.
  • Loh YH, Agarwal S, Park IH, Urbach A, Huo H, Heffner GC, Kim K, Miller JD, Ng K, Daley GQ. Generation of induced pluripotent stem cells from human blood. Blood. 2009 Mar 18. [Epub ahead of print] Read Abstract.
  • Milsom MD, Schiedlmeier B, Bailey J, Kim MO, Li D, Jansen M, Ali AM, Kirby M, Baum C, Fairbairn LJ, Williams DA. Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-{alpha} on Fanconi anemia hematopoietic stem and progenitor cells. Blood. 2009 Mar 6. [Epub ahead of print] Read Abstract.

Cancer

  • Lin HK, Wang G, Chen Z, Teruya-Feldstein J, Liu Y, Chan CH, Yang WL, Erdjument-Bromage H, Nakayama KI, Nimer S, Tempst P, Pandolfi PP. Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nat Cell Biol. 2009 Apr;11(4):420-32. Epub 2009 Mar 8. Read Abstract.
  • Mercher T, Raffel GD, Moore SA, Cornejo MG, Baudry-Bluteau D, Cagnard N, Jesneck JL, Pikman Y, Cullen D, Williams IR, Akashi K, Shigematsu H, Bourquin JP, Giovannini M, Vainchenker W, Levine RL, Lee BH, Bernard OA, Gilliland DG. The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model. J Clin Invest. 2009 Apr;119(4):852-64. doi: 10.1172/JCI35901. Epub 2009 Mar 16. Read Abstract.
  • Tefferi A, Levine RL, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Finke CM, Mullally A, Li CY, Pardanani A, Gilliland DG. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia. 2009 Mar 5. [Epub ahead of print] Read Abstract.
  • Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG, Levine RL. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 2009 Mar 19. [Epub ahead of print] Read Abstract.
  • Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009 Mar 5. [Epub ahead of print] Read Abstract.
  • Wojiski S, Guibal FC, Kindler T, Lee BH, Jesneck JL, Fabian A, Tenen DG, Gilliland DG. PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors. Leukemia. 2009 Mar 26. [Epub ahead of print] Read Abstract.

Cardiovascular System

  • Aikawa E, Aikawa M, Libby P, Figueiredo JL, Rusanescu G, Iwamoto Y, Fukuda D, Kohler RH, Shi GP, Jaffer FA, Weissleder R. Arterial and Aortic Valve Calcification Abolished by Elastolytic Cathepsin S Deficiency in Chronic Renal Disease. Circulation. 2009 Mar 23. [Epub ahead of print] Read Abstract.
  • Andersson KB, Birkeland JA, Finsen AV, Louch WE, Sjaastad I, Wang Y, Chen J, Molkentin JD, Chien KR, Sejersted OM, Christensen G. Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene. J Mol Cell Cardiol. 2009 Mar 25. [Epub ahead of print] Read Abstract.

Developmental Biology

  • Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009 Mar 20;136(6):1136-47. Read Abstract.
  • Hammell CM, Lubin I, Boag PR, Blackwell TK, Ambros V. nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell. 2009 Mar 6;136(5):926-38. Read Abstract.

Diabetes

  • Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton D. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol. 2009 Apr;5(4):258-65. Epub 2009 Mar 15. Read Abstract.

Genetics and Genomics

  • Kilpivaara O, Mukherjee S, Schram AM, Wadleigh M, Mullally A, Ebert BL, Bass A, Marubayashi S, Heguy A, Garcia-Manero G, Kantarjian H, Offit K, Stone RM, Gilliland DG, Klein RJ, Levine RL. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet. 2009 Apr;41(4):455-9. Epub 2009 Mar 15. Read Abstract.

Imaging

  • Christen T, Nahrendorf M, Wildgruber M, Swirski FK, Aikawa E, Waterman P, Shimizu K, Weissleder R, Libby P. Molecular Imaging of Innate Immune Cell Function in Transplant Rejection. Circulation. 2009 Mar 30. [Epub ahead of print] Read Abstract.
  • Koh I, Hong R, Weissleder R, Josephson L. Nanoparticle-Target Interactions Parallel Antibody-Protein Interactions. Anal Chem. 2009 Mar 26. [Epub ahead of print] Read Abstract.

Nervous System

  • Agalliu D, Takada S, Agalliu I, McMahon AP, Jessell TM. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009 Mar 12;61(5):708-20. Read Abstract.
  • Chung CY, Koprich JB, Siddiqi H, Isacson O. Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J Neurosci. 2009 Mar 18;29(11):3365-73. Read Abstract.
  • Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009 Mar 6;136(5):964-77. Read Abstract.
  • Zhang J, Xu TX, Hallett PJ, Watanabe M, Grant SG, Isacson O, Yao WD. PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex. J Neurosci. 2009 Mar 4;29(9):2948-60. Read Abstract.

Renal System

  • Bonventre JV. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant. 2009 Mar 23. [Epub ahead of print] Read Abstract.
  • Distefano G, Boca M, Rowe I, Claas W, Ma L, Piontek KB, Germino GG, Pandolfi PP Boletta A. Polycystin-1 Regulates ERKs-dependent Phosphorylation of Tuberin to Control Cell Size through mTOR and its Downstream Effectors S6K and 4EBP1. Mol Cell Biol. 2009 Mar 2. [Epub ahead of print] Read Abstract.

Skeletal System

  • Galli C, Fu Q, Wang W, Olsen BR, Manolagas SC, Jilka RL, O'Brien CA. Commitment to the osteoblast lineage is not required for rankl gene expression. J Biol Chem. 2009 Mar 11. [Epub ahead of print] Read Abstract.

Skin

  • Pietramaggiori G, Scherer SS, Alperovich M, Chen B, Orgill DP, Wagers AJ. Improved Cutaneous Healing in Diabetic Mice Exposed to Healthy Peripheral Circulation. J Invest Dermatol. 2009 Mar 19. [Epub ahead of print]

    Read Abstract.

Systems Biology

  • Mody A, Weiner J, Ramanathan S. Modularity of MAP kinases allows deformation of their signalling pathways. Nat Cell Biol. 2009 Apr;11(4):484-91. Epub 2009 Mar 22.

    Read Abstract.

Technology

  • Ball MP, Li JB, Gao Y, Lee JH, Leproust EM, Park IH, Xie B, Daley GQ, Church GM. Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol. 2009 Mar 29. [Epub ahead of print] Read Abstract.
  • Bassett EK, Slocum AH, Masiakos PT, Pryor HI 2nd, Farokhzad OC, Karp JM. Design of a mechanical clutch-based needle-insertion device. Proc Natl Acad Sci USA. 2009 Mar 23. [Epub ahead of print] Read Abstract.
  • Deng J, Shoemaker R, Xie B, Gore A, Leproust EM, Antosiewicz-Bourget J, Egli D, Maherali N, Park IH, Yu J, Daley GQ, Eggan K, Hochedlinger K, Thomson J, Wang W, Gao Y, Zhang K. Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming. Nat Biotechnol. 2009 Mar 29. [Epub ahead of print] Read Abstract.
  • Kim J, Cantor AB, Orkin SH, Wang J. Use of in vivo biotinylation to study protein-protein and protein-DNA interactions in mouse embryonic stem cells. Nat Protoc. 2009;4(4):506-17. Epub 2009 Mar 26. Read Abstract.
  • Wang J, Cantor AB, Orkin SH. Tandem affinity purification of protein complexes in mouse embryonic stem cells using in vivo biotinylation. Curr Protoc Stem Cell Biol 2009 Mar;Chapter 1:Unit1B.5. Read Abstract.