Research Newsletter - June 2010
Spotlight
In an article paper published in Nature biotechnology, HSCI Principal Faculty member Alex Meissner, PhD, and colleagues report their recent findings.
Dynamic single-cell imaging of direct reprogramming reveals an early specifying event
Abstract:
The study of induced pluripotency often relies on experimental approaches that average measurements across a large population of cells, the majority of which do not become pluripotent. Here we used high-resolution, time-lapse imaging to trace the reprogramming process over 2 weeks from single mouse embryonic fibroblasts (MEFs) to pluripotency factor-positive colonies. This enabled us to calculate a normalized cell-of-origin reprogramming efficiency that takes into account only the initial MEFs that respond to form reprogrammed colonies rather than the larger number of final colonies. Furthermore, this retrospective analysis revealed that successfully reprogramming cells undergo a rapid shift in their proliferative rate that coincides with a reduction in cellular area. This event occurs as early as the first cell division and with similar kinetics in all cells that form induced pluripotent stem (iPS) cell colonies. These data contribute to the theoretical modeling of reprogramming and suggest that certain parts of the reprogramming process follow defined rather than stochastic steps.
Smith ZD, Nachman I, Regev A, Meissner A. Dynamic single-cell imaging of direct reprogramming reveals an early specifying event. Nat Biotechnol. 2010 May;28(5):521-6. Epub 2010 May 2. Read Paper.
Review and Commentary
iPS Cells
Artyomov MN, Meissner A, Chakraborty AK. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency. PLoS Comput Biol. 2010 May 13;6(5):e1000785.
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Blood
Durand EM, Zon LI. Newly emerging roles for prostaglandin E2 regulation of hematopoiesis and hematopoietic stem cell engraftment. Curr Opin Hematol. 2010 May 13. [Epub ahead of print]
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Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall'Osso C, Wagers AJ, Huang PL, Rekhter M, Scalia R, Kahn CR, King GL. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell Metab. 2010 May 5;11(5):379-89.
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Tefferi A, Lasho TL, Abdel-Wahab O, Guglielmelli P, Patel J, Caramazza D, Pieri L, Finke CM, Kilpivaara O, Wadleigh M, Mai M, McClure RF, Gilliland DG, Levine RL, Pardanani A, Vannucchi AM. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia. 2010 May 27. [Epub ahead of print]
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Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, Takeuchi A, Grasemann C, Rinn JL, Lopez MF, Hirschhorn JN, Palmert MR, Daley GQ. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet. 2010 May 30. [Epub ahead of print]
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- Parmar K, Kim J, Sykes SM, Shimamura A, Stuckert P, Zhu K, Hamilton A, Deloach MK, Kutok JL, Akashi K, Gilliland DG, D'Andrea A. Hematopoietic Stem Cell Defects in Mice with Deficiency of Fancd2 or Usp1. Stem Cells. 2010 May 4. [Epub ahead of print] Read Abstract.
Cancer
Mullally A, Lane SW, Ball B, Megerdichian C, Okabe R, Al-Shahrour F, Paktinat M, Haydu JE, Housman E, Lord AM, Wernig G, Kharas MG, Mercher T, Kutok JL, Gilliland DG, Ebert BL. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell. 2010 Jun 15;17(6):584-96.
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Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a Dose of 25 mg Daily for Non-small Cell Lung Cancers with EGFR Mutations. J Thorac Oncol. 2010 May 27. [Epub ahead of print]
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Cardiovascular System
Ahmed S, Bu W, Lee RT, Maurer-Stroh S, Goh WI. F-BAR domain proteins: Families and function. Commun Integr Biol. 2010 Mar;3(2):116-21.
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Jiang B, Liao R. The Paradoxical Role of Inflammation in Cardiac Repair and Regeneration. J Cardiovasc Transl Res. 2010 May 7. [Epub ahead of print]
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Cell Biology
Prince RN, Schreiter ER, Zou P, Wiley HS, Ting AY, Lee RT, Lauffenburger DA. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release. J Cell Sci. 2010 Jul 1;123(Pt 13):2308-18. Epub 2010 Jun 8.
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Developmental Biology
Egli D, Eggan K. Recipient cell nuclear factors are required for reprogramming by nuclear transfer. Development. 2010 Jun;137(12):1953-63. Epub 2010 May 12.
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Lee EY, Ji H, Ouyang Z, Zhou B, Ma W, Vokes SA, McMahon AP, Wong WH, Scott MP. Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9736-41. Epub 2010 May 11.
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Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development. 2010 May;137(10):1721-9.
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Rodin S, Domogatskaya A, Ström S, Hansson EM, Chien KR, Inzunza J, Hovatta O, Tryggvason K. Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511. Nat Biotechnol. 2010 Jun;28(6):611-5. Epub 2010 May 30.
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Diabetes
Shoda L, Kreuwel H, Gadkar K, Zheng Y, Whiting C, Atkinson M, Bluestone J, Mathis D, Young D, Ramanujan S. The Type 1 Diabetes PhysioLab Platform: a validated physiologically based mathematical model of pathogenesis in the non-obese diabetic mouse. Clin Exp Immunol. 2010 May 18. [Epub ahead of print]
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Suwanai H, Wilcox MA, Mathis D, Benoist C. A defective Il15 allele underlies the deficiency in natural killer cell activity in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9305-10. Epub 2010 May 3.
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Genetics and Genomics
Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell. 2010 May 7;6(5):407-11.
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Williams DA, Cook AL. An infant with Williams-Beuren syndrome and Ebstein anomaly. Cardiol Young. 2010 May 14:1-3. [Epub ahead of print]
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Imaging
Smith ZD, Nachman I, Regev A, Meissner A. Dynamic single-cell imaging of direct reprogramming reveals an early specifying event. Nat Biotechnol. 2010 May;28(5):521-6. Epub 2010 May 2.
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Immunology
Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and MF arise from distinct T cell subsets: a biologic rationale for their distinct clinical behaviors. Blood. 2010 May 18. [Epub ahead of print]
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Iwai LK, Benoist C, Mathis D, White FM. Quantitative Phosphoproteomic Analysis of T Cell Receptor Signaling in Diabetes Prone and Resistant Mice. J Proteome Res. 2010 May 18. [Epub ahead of print]
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Zhang W, Choi J, Zeng W, Rogers SA, Alyea EP, Rheinwald JG, Canning CM, Brusic V, Sasada T, Reinherz EL, Ritz J, Soiffer RJ, Wu CJ. Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. Clin Cancer Res. 2010 May 15;16(10):2729-39. Epub 2010 May 11.
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Muscular System
Kang PB, Lidov HG, White AJ, Mitchell M, Balasubramanian A, Estrella E, Bennett RR, Darras BT, Shapiro FD, Bambach BJ, Kurtzberg J, Gussoni E, Kunkel LM. Inefficient dystrophin expression after cord blood transplantation in Duchenne muscular dystrophy. Muscle Nerve. 2010 Jun;41(6):746-50.
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Nervous System
Cubelos B, Sebastián-Serrano A, Beccari L, Calcagnotto ME, Cisneros E, Kim S, Dopazo A, Alvarez-Dolado M, Redondo JM, Bovolenta P, Walsh CA, Nieto M. Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex. Neuron. 2010 May 27;66(4):523-35.
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Renal System
Bonventre JV, Vaidya VS, Schmouder R, Feig P, Dieterle F. Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol. 2010 May;28(5):436-40.
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Heher EC, Goes NB, Spitzer TR, Raje NS, Humphreys BD, Anderson KC, Richardson PG. Kidney disease associated with plasma cell dyscrasias. Blood. 2010 May 12. [Epub ahead of print]
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Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010 May;28(5):478-85.
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Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med. 2010 May;16(5):535-43, 1p following 143. Epub 2010 May 2.
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Skin
Kabbarah O, Nogueira C, Feng B, Nazarian RM, Bosenberg M, Wu M, Scott KL, Kwong LN, Xiao Y, Cordon-Cardo C, Granter SR, Ramaswamy S, Golub T, Duncan LM, Wagner SN, Brennan C, Chin L. Integrative genome comparison of primary and metastatic melanomas. PLoS One. 2010 May 24;5(5):e10770.
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Tissue Engineering
Göktepe S, Abilez OJ, Parker KK, Kuhl E. A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. J Theor Biol. 2010 May 4. [Epub ahead of print]
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Hoganson DM, Pryor HI 2nd, Spool ID, Burns OH, Gilmore JR, Vacanti JP. Principles of biomimetic vascular network design applied to a tissue-engineered liver scaffold. Tissue Eng Part A. 2010 May;16(5):1469-77.
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