Research Newsletter - January 2009

Spotlight

In an article paper published in Nature, HSCI Co-Director David Scadden and colleagues report on the live-animal tracking of individual haematopoietic stem/progenitor cells in their niche.

Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche

Abstract:

Stem cells reside in a specialized, regulatory environment termed the niche that dictates how they generate, maintain and repair tissues. We have previously documented that transplanted haematopoietic stem and progenitor cell populations localize to subdomains of bone-marrow microvessels where the chemokine CXCL12 is particularly abundant. Using a combination of high-resolution confocal microscopy and two-photon video imaging of individual haematopoietic cells in the calvarium bone marrow of living mice over time, we examine the relationship of haematopoietic stem and progenitor cells to blood vessels, osteoblasts and endosteal surface as they home and engraft in irradiated and c-Kit-receptor-deficient recipient mice. Osteoblasts were enmeshed in microvessels and relative positioning of stem/progenitor cells within this complex tissue was nonrandom and dynamic. Both cell autonomous and non-autonomous factors influenced primitive cell localization. Different haematopoietic cell subsets localized to distinct locations according to the stage of differentiation. When physiological challenges drove either engraftment or expansion, bone-marrow stem/progenitor cells assumed positions in close proximity to bone and osteoblasts. Our analysis permits observing in real time, at a single cell level, processes that previously have been studied only by their long-term outcome at the organismal level.

Lo Celso C, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, Côté D, Rowe DW, Lin CP, Scadden DT. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009 Jan 1;457(7225):92-6. Epub 2008 Dec 3. Read paper.

Scientific Papers

Review and Commentary

  • Hyun I, Lindvall O, Ahrlund-Richter L, Cattaneo E, Cavazzana-Calvo M, Cossu G, De Luca M, Fox IJ, Gerstle C, Goldstein RA, Hermerén G, High KA, Kim HO, Lee HP, Levy-Lahad E, Li L, Lo B, Marshak DR, McNab A, Munsie M, Nakauchi H, Rao M, Rooke HM, Valles CS, Srivastava A, Sugarman J, Taylor PL, Veiga A, Wong AL, Zoloth L, Daley GQ. New ISSCR guidelines underscore major principles for responsible translational stem cell research. Cell Stem Cell. 2008 Dec 4;3(6):607-9. Review.

    Read Abstract.
  • Ceol CJ, Houvras Y, White RM, Zon LI. Melanoma biology and the promise of zebrafish. Zebrafish. 2008 Dec;5(4):247-55. Read Abstract.
  • Chien KR, Domian IJ, Parker KK. Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science. 2008 Dec 5;322(5907):1494-7. Review. Read Abstract.
  • Gunaratnam L, Bonventre JV. HIF in Kidney Disease and Development. J Am Soc Nephrol. 2008 Dec 31. [Epub ahead of print] Read Abstract.
  • Gurdon JB, Melton DA. Nuclear reprogramming in cells. Science. 2008 Dec 19;322(5909):1811-5. Review. Read Abstract.
  • Hedlund E, Isacson O. ALS model glia can mediate toxicity to motor neurons derived from human embryonic stem cells. Cell Stem Cell. 2008 Dec 4;3(6):575-6. Review. Read Abstract.
  • Maherali N, Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell. 2008 Dec 4;3(6):595-605. Review. Read Abstract.
  • Raaijmakers MH, Scadden DT. Divided within: heterogeneity within adult stem cell pools. Cell. 2008 Dec 12;135(6):1006-8. Read Abstract.

Aging

  • Oláhová M, Taylor SR, Khazaipoul S, Wang J, Morgan BA, Matsumoto K, Blackwell TK, Veal EA. A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Proc Natl Acad Sci USA. 2008 Dec 16;105(50):19839-44. Epub 2008 Dec 8.

    Read Abstract.

Blood

  • Faber J, Krivtsov AV, Stubbs MC, Wright R, Davis TN, van den Heuvel-Eibrink M, Zwaan CM, Kung AL, Armstrong SA. HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood. 2008 Dec 3. [Epub ahead of print] Read Abstract.
  • Fraenkel PG, Gibert Y, Holzheimer JL, Lattanzi VJ, Burnett SF, Dooley KA, Wingert RA, Zon LI. Transferrin-a modulates hepcidin expression in zebrafish embryos. Blood. 2008 Dec 1. [Epub ahead of print] Read Abstract.
  • Sankaran VG, Menne TF, Xu J, Akie TE, Lettre G, Van Handel B, Mikkola HK, Hirschhorn JN, Cantor AB, Orkin SH. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008 Dec 19;322(5909):1839-42. Epub 2008 Dec 4. Read Abstract.
  • Tyner JW, Erickson H, Deininger MW, Willis SG, Eide CA, Levine RL, Heinrich MC, Gattermann N, Gilliland DG, Druker BJ, Loriaux MM. High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients. Blood. 2008 Dec 15. [Epub ahead of print] Read Abstract.

Cancer

  • Carracedo A, Baselga J, Pandolfi PP. Deconstructing feedback-signaling networks to improve anticancer therapy with mTORC1 inhibitors. Cell Cycle. 2008 Dec 22;7(24). [Epub ahead of print] Read Abstract.
  • Gan B, Sahin E, Jiang S, Sanchez-Aguilera A, Scott KL, Chin L, Williams DA, Kwiatkowski DJ, DePinho RA. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc Natl Acad Sci USA. 2008 Dec 9;105(49):19384-9. Epub 2008 Dec 3. Read Abstract.
  • Jeong JH, Wang Z, Guimaraes AS, Ouyang X, Figueiredo JL, Ding Z, Jiang S, Guney I, Kang GH, Shin E, Hahn WC, Loda MF, Abate-Shen C, Weissleder R, Chin L. BRAF activation initiates but does not maintain invasive prostate adenocarcinoma. PLoS ONE. 2008;3(12):e3949. Epub 2008 Dec 16. Read Abstract.
  • Koschmieder S, Halmos B, Levantini E, Tenen DG. Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer. J Clin Oncol. 2008 Dec 15. [Epub ahead of print] Read Abstract.
  • Lage K, Hansen NT, Karlberg EO, Eklund AC, Roque FS, Donahoe PK, Szallasi Z, Jensen TS, Brunak S. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc Natl Acad Sci USA. 2008 Dec 30;105(52):20870-5. Epub 2008 Dec 22. Read Abstract.
  • Lapi E, Di Agostino S, Donzelli S, Gal H, Domany E, Rechavi G, Pandolfi PP, Givol D, Strano S, Lu X, Blandino G. PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop. Mol Cell. 2008 Dec 26;32(6):803-14. Read Abstract.

Cardiovascular System

  • Hoenig MR, Bianchi C, Rosenzweig A, Sellke FW. Decreased vascular repair and neovascularization with ageing: mechanisms and clinical relevance with an emphasis on hypoxia-inducible factor-1. Curr Mol Med. 2008 Dec;8(8):754-67. Read Abstract.
  • Liu X, Ramjiganesh T, Chen YH, Chung SW, Hall SR, Schissel SL, Padera RF Jr, Liao R, Ackerman KG, Kajstura J, Leri A, Anversa P, Yet SF, Layne MD, Perrella MA. Disruption of Striated Preferentially Expressed Gene Locus Leads to Dilated Cardiomyopathy in Mice. Circulation. 2008 Dec 31. [Epub ahead of print] Read Abstract.
  • Risebro CA, Searles RG, Melville AA, Ehler E, Jina N, Shah S, Pallas J, Hubank M, Dillard M, Harvey NL, Schwartz RJ, Chien KR, Oliver G, Riley PR. Prox1 maintains muscle structure and growth in the developing heart. Development. 2008 Dec 17. [Epub ahead of print] Read Abstract.

Developmental Biology

  • de Campos-Baptista MI, Holtzman NG, Yelon D, Schier AF. Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish. Dev Dyn. 2008 Dec;237(12):3624-33. Read Abstract.
  • Foudi A, Hochedlinger K, Van Buren D, Schindler JW, Jaenisch R, Carey V, Hock H. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol. 2009 Jan;27(1):84-90. Epub 2008 Dec 5. Read Abstract.
  • Huang Z, Kawase-Koga Y, Zhang S, Visvader J, Toth M, Walsh CA, Sun T. Transcription factor Lmo4 defines the shape of functional areas in developing cortices and regulates sensorimotor control. Dev Biol. 2008 Dec 16. [Epub ahead of print] Read Abstract.

Diabetes

  • Inada A, Nienaber C, Katsuta H, Fujitani Y, Levine J, Morita R, Sharma A, Bonner-Weir S. Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc Natl Acad Sci USA. 2008 Dec 16;105(50):19915-9. Epub 2008 Dec 3. Read Abstract.

Genetics and Genomics

  • Zimmer M, Ebert BL, Neil C, Brenner K, Papaioannou I, Melas A, Tolliday N, Lamb J, Pantopoulos K, Golub T, Iliopoulos O. Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing. Mol Cell. 2008 Dec 26;32(6):838-48. Read Abstract.

Imaging

  • Devaraj NK, Weissleder R, Hilderbrand SA. Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjug Chem. 2008 Dec;19(12):2297-9. Read Abstract.
  • Garanger E, Weissleder R, Josephson L. A Multifunctional Single-Attachment-Point Reagent for Controlled Protein Biotinylation. Bioconjug Chem. 2008 Dec 11. [Epub ahead of print] Read Abstract.
  • Salthouse C, Hildebrand S, Weissleder R, Mahmood U. Design and demonstration of a small-animal up-conversion imager. Opt Express. 2008 Dec 22;16(26):21731-7. Read Abstract.
  • Shao F, Weissleder R, Hilderbrand SA. Monofunctional carbocyanine dyes for bio- and bioorthogonal conjugation. Bioconjug Chem. 2008 Dec;19(12):2487-91. Read Abstract.

Immunology

  • D'Alise AM, Auyeung V, Feuerer M, Nishio J, Fontenot J, Benoist C, Mathis D. The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc Natl Acad Sci USA. 2008 Dec 16;105(50):19857-62. Epub 2008 Dec 10. Read Abstract.
  • Hartner JC, Walkley CR, Lu J, Orkin SH. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol. 2009 Jan;10(1):109-15. Epub 2008 Dec 7. Read Abstract.
  • Patel NC, Chinen J, Rosenblatt HM, Hanson IC, Brown BS, Paul ME, Abramson SL, Ritz J, Shearer WT. Long-term outcomes of nonconditioned patients with severe combined immunodeficiency transplanted with HLA-identical or haploidentical bone marrow depleted of T cells with anti-CD6 mAb. J Allergy Clin Immunol. 2008 Dec;122(6):1185-93. Read Abstract.

Nervous System

  • Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ, Samad TA. Nociceptors are interleukin-1beta sensors. J Neurosci. 2008 Dec 24;28(52):14062-73. Read Abstract.
  • Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell. 2008 Dec 4;3(6):637-48. Read Abstract.
  • Punzo C, Kornacker K, Cepko CL. Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa. Nat Neurosci. 2009 Jan;12(1):44-52. Epub 2008 Dec 7. Read Abstract.

Pulmonary System

  • Kim KK, Wei Y, Szekeres C, Kugler MC, Wolters PJ, Hill ML, Frank JA, Brumwell AN, Wheeler SE, Kreidberg JA, Chapman HA. Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. J Clin Invest. 2009 Jan;119(1):213-24. doi: 10.1172/JCI36940. Epub 2008 Dec 22. Read Abstract.

Renal System

  • Kim J, Kim KY, Jang HS, Yoshida T, Tsuchiya K, Nitta K, Park JW, Bonventre JV, Park KM. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia/reperfusion injury in mouse kidney. Am J Physiol Renal Physiol. 2008 Dec 23. [Epub ahead of print] Read Abstract.

Skin

  • Jin H, Oyoshi MK, Le Y, Bianchi T, Koduru S, Mathias CB, Kumar L, Le Bras S, Young D, Collins M, Grusby MJ, Wenzel J, Bieber T, Boes M, Silberstein LE, Oettgen HC, Geha RS. IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. J Clin Invest. 2009 Jan;119(1):47-60. doi: 10.1172/JCI32310. Epub 2008 Dec 15. Read Abstract.

Technology

  • Carraro A, Hsu WM, Kulig KM, Cheung WS, Miller ML, Weinberg EJ, Swart EF, Kaazempur-Mofrad M, Borenstein JT, Vacanti JP, Neville C. In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices. 2008 Dec;10(6):795-805. Read Abstract.
  • Donahoe PK, Noonan KM, Lage K. Genetic tools and algorithms for gene discovery in major congenital anomalies. Birth Defects Res A Clin Mol Teratol. 2008 Dec 23;85(1):6-12. [Epub ahead of print] No abstract available. Read Abstract.
  • Lo Celso C, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, C√¥t√© D, Rowe DW, Lin CP, Scadden DT. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009 Jan 1;457(7225):92-6. Epub 2008 Dec 3. Read Abstract.
  • Sessa AK, White R, Houvras Y, Burke C, Pugach E, Baker B, Gilbert R, Thomas Look A, Zon LI. The effect of a depth gradient on the mating behavior, oviposition site preference, and embryo production in the zebrafish, Danio rerio. Zebrafish. 2008 Dec;5(4):335-9. Read Abstract.
  • Sommer CA, Stadtfeld M, Murphy GJ, Hochedlinger K, Kotton DN, Mostoslavsky G. iPS Cell Generation Using a Single Lentiviral Stem Cell Cassette. Stem Cells. 2008 Dec 18. [Epub ahead of print] Read Abstract.

Tissue Engineering

  • Sun XD, Jeng L, Bolliet C, Olsen BR, Spector M. Non-viral endostatin plasmid transfection of mesenchymal stem cells via collagen scaffolds. Biomaterials. 2009 Feb;30(6):1222-31. Epub 2008 Dec 6. Read Abstract.