Research Newsletter - May 2010
Spotlight
In an article paper published in Nature, HSCI Principal Faculty member Konrad Hochedlinger, PhD, and colleagues report their recent findings.
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Abstract
Induced pluripotent stem cells (iPSCs) have been generated by enforced expression of defined sets of transcription factors in somatic cells. It remains controversial whether iPSCs are molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells. By comparing genetically identical mouse ES cells and iPSCs, we show here that their overall messenger RNA and microRNA expression patterns are indistinguishable with the exception of a few transcripts encoded within the imprinted Dlk1-Dio3 gene cluster on chromosome 12qF1, which were aberrantly silenced in most of the iPSC clones. Consistent with a developmental role of the Dlk1-Dio3 gene cluster, these iPSC clones contributed poorly to chimaeras and failed to support the development of entirely iPSC-derived animals ('all-iPSC mice'). In contrast, iPSC clones with normal expression of the Dlk1-Dio3 cluster contributed to high-grade chimaeras and generated viable all-iPSC mice. Notably, treatment of an iPSC clone that had silenced Dlk1-Dio3 with a histone deacetylase inhibitor reactivated the locus and rescued its ability to support full-term development of all-iPSC mice. Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells.
Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature. 2010 May 13;465(7295):175-81. Epub 2010 Apr 25. Read Paper.
Review and Commentary
Bejar R, Ebert BL. The genetic basis of myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010 Apr;24(2):295-315.
Read Abstract.
Bonventre JV. Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol. 2010;165:9-17. Epub 2010 Apr 20.
Read Abstract.
Ebert BL. Preface. The biology and treatment of myelodysplastic syndrome. Hematol Oncol Clin North Am. 2010 Apr;24(2):xiii-xvi.
Read Abstract.
Ikeda S, Pu WT. Expression and Function of MicroRNAs in Heart Disease. Curr Drug Targets. 2010 Apr 26. [Epub ahead of print]
Read Abstract.
iPS Cells
Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature. 2010 May 13;465(7295):175-81. Epub 2010 Apr 25.
Read Abstract.
Blood
de Jong JL, Davidson AJ, Wang Y, Palis J, Opara P, Pugach E, Daley GQ, Zon LI. Interaction of retinoic acid and scl controls primitive blood development. Blood. 2010 Apr 21. [Epub ahead of print]
Read Abstract.
Cancer
Aikawa Y, Katsumoto T, Zhang P, Shima H, Shino M, Terui K, Ito E, Ohno H, Stanley ER, Singh H, Tenen DG, Kitabayashi I. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med. 2010 May;16(5):580-5, 1p following 585. Epub 2010 Apr 25.
Read Abstract.
Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, Egia A, Salmena L, Sampieri K, Haveman WJ, Brogi E, Richardson AL, Zhang J, Pandolfi PP. Subtle variations in Pten dose determine cancer susceptibility. Nat Genet. 2010 May;42(5):454-8. Epub 2010 Apr 18.
Read Abstract.
Chan CH, Lee SW, Li CF, Wang J, Yang WL, Wu CY, Wu J, Nakayama KI, Kang HY, Huang HY, Hung MC, Pandolfi PP, Lin HK. Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis. Nat Cell Biol. 2010 May;12(5):457-67. Epub 2010 Apr 11.
Read Abstract.
Jo H, Loison F, Hattori H, Silberstein LE, Yu H, Luo HR. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs. PLoS One. 2010 Apr 23;5(4):e10318.
Read Abstract.
Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, Hobbs RM, Sportoletti P, Varmeh S, Egia A, Fedele G, Rameh L, Loda M, Pandolfi PP. Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal. 2010 Apr 13;3(117):ra29.
Read Abstract.
Pulikkan JA, Dengler V, Peer Zada AA, Kawasaki A, Geletu M, Pasalic Z, Bohlander SK, Ryo A, Tenen DG, Behre G. Elevated PIN1 expression by C/EBPalpha-p30 blocks C/EBPalpha-induced granulocytic differentiation through c-Jun in AML. Leukemia. 2010 May;24(5):914-23. Epub 2010 Apr 8.
Read Abstract.
Sengupta A, Arnett J, Dunn S, Williams DA, Cancelas JA. Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. Blood. 2010 Apr 20. [Epub ahead of print]
Read Abstract.
Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010 Apr 2;141(1):69-80. Read Abstract.
Cardiovascular System
Panizzi P, Swirski FK, Figueiredo JL, Waterman P, Sosnovik DE, Aikawa E, Libby P, Pittet M, Weissleder R, Nahrendorf M. Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis. J Am Coll Cardiol. 2010 Apr 13;55(15):1629-38.
Read Abstract.
Developmental Biology
Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, Chen X, Mukaddes NM, Yoo SY, Hanson E, Hundley R, Austin C, Becker RE, Berry GT, Driscoll K, Engle EC, Friedman S, Gusella JF, Hisama FM, Irons MB, Lafiosca T, Leclair E, Miller DT, Neessen M, Picker JD, Rappaport L, Rooney CM, Sarco DP, Stoler JM, Walsh CA, Wolff RR, Zhang T, Nasir RH, Wu BL; on behalf of the Children's Hospital Boston Genotype Phenotype Study GroupThe Children's Hospital Boston Genotype Phenotype Study Group also includes Omar S. Khwaja, Annapurna Poduri, Mustafa Sahin and Magdi Sobeih, Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts.. Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 7. [Epub ahead of print]
Read Abstract.
Davidson AJ, Ellis MJ, Chaudhuri JB. A theoretical method to improve and optimize the design of bioartificial livers. Biotechnol Bioeng. 2010 Apr 16. [Epub ahead of print]
Read Abstract.
Harvey SA, Tümpel S, Dubrulle J, Schier AF, Smith JC. no tail integrates two modes of mesoderm induction. Development. 2010 Apr;137(7):1127-35.
Read Abstract.
Rompani SB, Cepko CL. A common progenitor for retinal astrocytes and oligodendrocytes. J Neurosci. 2010 Apr 7;30(14):4970-80.
Read Abstract.
Trowbridge JJ, Orkin SH. DNA methylation in adult stem cells: New insights into self-renewal. Epigenetics. 2010 Apr 31;5(3). [Epub ahead of print]
Read Abstract.
van Aelst K, Tóth J, Ramanathan SP, Schwarz FW, Seidel R, Szczelkun MD. Type III restriction enzymes cleave DNA by long-range interaction between sites in both head-to-head and tail-to-tail inverted repeat. Proc Natl Acad Sci U S A. 2010 Apr 30. [Epub ahead of print]
Read Abstract.
Xu J, Sankaran VG, Ni M, Menne TF, Puram RV, Kim W, Orkin SH. Transcriptional silencing of {gamma}-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev. 2010 Apr 15;24(8):783-98.
Read Abstract.
Diabetes
Igoillo-Esteve M, Marselli L, Cunha DA, Ladrière L, Ortis F, Grieco FA, Dotta F, Weir GC, Marchetti P, Eizirik DL, Cnop M. Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia. 2010 Apr 6. [Epub ahead of print]
Read Abstract.
Imaging
Bratlie KM, Dang TT, Lyle S, Nahrendorf M, Weissleder R, Langer R, Anderson DG. Rapid biocompatibility analysis of materials via in vivo fluorescence imaging of mouse models. PLoS One. 2010 Apr 6;5(4):e10032.
Read Abstract.
Nahrendorf M, Keliher E, Marinelli B, Waterman P, Feruglio PF, Fexon L, Pivovarov M, Swirski FK, Pittet MJ, Vinegoni C, Weissleder R. Hybrid PET-optical imaging using targeted probes. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7910-5. Epub 2010 Apr 12.
Read Abstract.
Vinegoni C, Fumene Feruglio P, Cortez-Retamozo V, Razansky D, Medoff BD, Ntziachristos V, Sbarbati A, Pittet M, Weissleder R. Imaging of molecular probe activity with Born-normalized fluorescence optical projection tomography. Opt Lett. 2010 Apr 1;35(7):1088-90. doi: 10.1364/OL.35.001088.
Read Abstract.
Immunology
Jiang X, Campbell JJ, Kupper TS. Embryonic trafficking of gammadelta T cells to skin is dependent on E/P selectin ligands and CCR4. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7443-8. Epub 2010 Apr 5.
Read Abstract.
Kaieda S, Shin K, Nigrovic PA, Seki K, Lee RT, Stevens RL, Lee DM. Synovial fibroblasts promote the expression and granule accumulation of tryptase via interleukin-33 and its receptor ST-2 (IL1RL1). J Biol Chem. 2010 Apr 28. [Epub ahead of print]
Read Abstract.
Matsuoka K, Kim HT, McDonough S, Bascug G, Warshauer B, Koreth J, Cutler C, Ho VT, Alyea EP, Antin JH, Soiffer RJ, Ritz J. Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation. J Clin Invest. 2010 May 3;120(5):1479-93. doi: 10.1172/JCI41072. Epub 2010 Apr 12.
Read Abstract.
Nervous System
Kim DS, Lee JS, Leem JW, Huh YJ, Kim JY, Kim HS, Park IH, Daley GQ, Hwang DY, Kim DW. Erratum to: Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity. Stem Cell Rev. 2010 Apr 23. [Epub ahead of print]
Read Abstract.
Kim DS, Lee JS, Leem JW, Huh YJ, Kim JY, Kim HS, Park IH, Daley GQ, Hwang DY, Kim DW. Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity. Stem Cell Rev. 2010 Apr 8. [Epub ahead of print]
Read Abstract.
Kim S, Lehtinen MK, Sessa A, Zappaterra MW, Cho SH, Gonzalez D, Boggan B, Austin CA, Wijnholds J, Gambello MJ, Malicki J, LaMantia AS, Broccoli V, Walsh CA. The apical complex couples cell fate and cell survival to cerebral cortical development. Neuron. 2010 Apr 15;66(1):69-84.
Read Abstract.
Manzini MC, Rajab A, Maynard TM, Mochida GH, Tan WH, Nasir R, Hill RS, Gleason D, Al Saffar M, Partlow JN, Barry BJ, Vernon M, LaMantia AS, Walsh CA. Developmental and degenerative features in a complicated spastic paraplegia. Ann Neurol. 2010 Apr;67(4):516-25.
Read Abstract.
Silver DL, Watkins-Chow DE, Schreck KC, Pierfelice TJ, Larson DM, Burnetti AJ, Liaw HJ, Myung K, Walsh CA, Gaiano N, Pavan WJ. The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci. 2010 May;13(5):551-8. Epub 2010 Apr 4.
Read Abstract.
Renal System
Hartwig S, Ho J, Pandey P, Macisaac K, Taglienti M, Xiang M, Alterovitz G, Ramoni M, Fraenkel E, Kreidberg JA. Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development. Development. 2010 Apr;137(7):1189-203.
Read Abstract.
Tissue Engineering
Bray MA, Adams WJ, Geisse NA, Feinberg AW, Sheehy SP, Parker KK. Nuclear morphology and deformation in engineered cardiac myocytes and tissues. Biomaterials. 2010 Jul;31(19):5143-50. Epub 2010 Apr 10.
Read Abstract.
Translational Medicine
Hingtgen SD, Kasmieh R, van de Water J, Weissleder R, Shah K. A novel molecule integrating therapeutic and diagnostic activities reveals multiple aspects of stem cell-based therapy. Stem Cells. 2010 Apr;28(4):832-41.
Read Abstract.
Sarkar D, Vemula PK, Zhao W, Gupta A, Karnik R, Karp JM . Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting. Biomaterials. 2010 Jul;31(19):5266-74. Epub 2010 Apr 8.
Read Abstract.
