Now showing items 1-20 of 27

    • Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling 

      Lin, Michelle I; Price, Emily N; Boatman, Sonja; Hagedorn, Elliott J; Trompouki, Eirini; Satishchandran, Sruthi; Carspecken, Charles W; Uong, Audrey; DiBiase, Anthony; Yang, Song; Canver, Matthew C; Dahlberg, Ann; Lu, Zhigang; Zhang, Cheng Cheng; Orkin, Stuart H; Bernstein, Irwin D; Aster, Jon C; White, Richard M; Zon, Leonard I (eLife Sciences Publications, Ltd, 2015)
      Angiopoietin-like proteins (angptls) are capable of ex vivo expansion of mouse and human hematopoietic stem and progenitor cells (HSPCs). Despite this intriguing ability, their mechanism is unknown. In this study, we show ...
    • CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types 

      Nelms, Bradlee D.; Waldron, Levi; Barrera, Luis A.; Weflen, Andrew W.; Goettel, Jeremy A.; Guo, Guoji; Montgomery, Robert K.; Neutra, Marian R.; Breault, David T.; Snapper, Scott B.; Orkin, Stuart H.; Bulyk, Martha L.; Huttenhower, Curtis; Lencer, Wayne I. (BioMed Central, 2016)
      We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our ...
    • Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis 

      Saadatpour, Assieh; Guo, Guoji; Orkin, Stuart H; Yuan, Guo-Cheng (BioMed Central, 2014)
      Background: A fundamental challenge for cancer therapy is that each tumor contains a highly heterogeneous cell population whose structure and mechanistic underpinnings remain incompletely understood. Recent advances in ...
    • A Comparative Encyclopedia of DNA Elements in the Mouse Genome 

      Yue, Feng; Cheng, Yong; Breschi, Alessandra; Vierstra, Jeff; Wu, Weisheng; Ryba, Tyrone; Sandstrom, Richard; Ma, Zhihai; Davis, Carrie; Pope, Benjamin D.; Shen, Yin; Pervouchine, Dmitri D.; Djebali, Sarah; Thurman, Bob; Kaul, Rajinder; Rynes, Eric; Kirilusha, Anthony; Marinov, Georgi K.; Williams, Brian A.; Trout, Diane; Amrhein, Henry; Fisher-Aylor, Katherine; Antoshechkin, Igor; DeSalvo, Gilberto; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Zaleski, Chris; Dobin, Alex; Prieto, Pablo; Lagarde, Julien; Bussotti, Giovanni; Tanzer, Andrea; Denas, Olgert; Li, Kanwei; Bender, M. A.; Zhang, Miaohua; Byron, Rachel; Groudine, Mark T.; McCleary, David; Pham, Long; Ye, Zhen; Kuan, Samantha; Edsall, Lee; Wu, Yi-Chieh; Rasmussen, Matthew D.; Bansal, Mukul S.; Keller, Cheryl A.; Morrissey, Christapher S.; Mishra, Tejaswini; Jain, Deepti; Dogan, Nergiz; Harris, Robert S.; Cayting, Philip; Kawli, Trupti; Boyle, Alan P.; Euskirchen, Ghia; Kundaje, Anshul; Lin, Shin; Lin, Yiing; Jansen, Camden; Malladi, Venkat S.; Cline, Melissa S.; Erickson, Drew T.; Kirkup, Vanessa M; Learned, Katrina; Sloan, Cricket A.; Rosenbloom, Kate R.; de Sousa, Beatriz Lacerda; Beal, Kathryn; Pignatelli, Miguel; Flicek, Paul; Lian, Jin; Kahveci, Tamer; Lee, Dongwon; Kent, W. James; Santos, Miguel Ramalho; Herrero, Javier; Notredame, Cedric; Johnson, Audra; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Canfield, Theresa; Sabo, Peter J.; Wilken, Matthew S.; Reh, Thomas A.; Giste, Erika; Shafer, Anthony; Kutyavin, Tanya; Haugen, Eric; Dunn, Douglas; Reynolds, Alex P.; Neph, Shane; Humbert, Richard; Hansen, R. Scott; De Bruijn, Marella; Selleri, Licia; Rudensky, Alexander; Josefowicz, Steven; Samstein, Robert; Eichler, Evan E.; Orkin, Stuart H.; Levasseur, Dana; Papayannopoulou, Thalia; Chang, Kai-Hsin; Skoultchi, Arthur; Gosh, Srikanta; Disteche, Christine; Treuting, Piper; Wang, Yanli; Weiss, Mitchell J.; Blobel, Gerd A.; Good, Peter J.; Lowdon, Rebecca F.; Adams, Leslie B.; Zhou, Xiao-Qiao; Pazin, Michael J.; Feingold, Elise A.; Wold, Barbara; Taylor, James; Kellis, Manolis; Mortazavi, Ali; Weissman, Sherman M.; Stamatoyannopoulos, John; Snyder, Michael P.; Guigo, Roderic; Gingeras, Thomas R.; Gilbert, David M.; Hardison, Ross C.; Beer, Michael A.; Ren, Bing (2014)
      Summary As the premier model organism in biomedical research, the laboratory mouse shares the majority of protein-coding genes with humans, yet the two mammals differ in significant ways. To gain greater insights into both ...
    • Dissecting Molecular Similarities and Differences Between Pluripotent Stem Cell Lines 

      Choi, Jiho (2015-05-16)
      Traditionally, pluripotent stem cells are derived from preimplantation embryos and fetal germ cells, which give rise to embryonic stem cells (ESCs) and embryonic germ cells (EGCs), respectively, In contrast, induced ...
    • Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation 

      Foudi, Adlen; Kramer, Daniel J.; Qin, Jinzhong; Ye, Denise; Behlich, Anna-Sophie; Mordecai, Scott; Preffer, Frederic I.; Amzallag, Arnaud; Ramaswamy, Sridhar; Hochedlinger, Konrad; Orkin, Stuart H.; Hock, Hanno (The Rockefeller University Press, 2014)
      The zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. ...
    • Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine 

      Kim, Jonghwan; Orkin, Stuart Holland (BioMed Central, 2011)
      Embryonic stem (ES) cells are of great interest as a model system for studying early developmental processes and because of their potential therapeutic applications in regenerative medicine. Obtaining a systematic understanding ...
    • Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia 

      Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Zhang, Xi; Haladyna, Jessica N.; Riedel, Simone S.; Zhu, Nan; Xie, Huafeng; Orkin, Stuart H.; Armstrong, Scott A.; Bernt, Kathrin M.; Neff, Tobias (2016)
      SUMMARY Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive ...
    • Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence 

      Kim, Peter Geon; Nakano, Haruko; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Sakamoto, Kathleen M.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Nakano, Atsushi; Daley, George Q. (The Rockefeller University Press, 2015)
      Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta–gonad–mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein ...
    • GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia 

      Maroz, Aliaksandra; Stachorski, Lena; Emmrich, Stephan; Reinhardt, Katarina; Xu, Jian; Shao, Zhen; Käbler, Sebastian; Dertmann, Tobias; Hitzler, Johann; Roberts, Irene; Vyas, Paresh; Juban, Gaetan; Hennig, Christian; Hansen, Gesine; Li, Zhe; Orkin, Stuart; Reinhardt, Dirk; Klusmann, Jan-Henning (2014)
      Transient leukemia (TL) is evident in 5–10% of all neonates with Down syndrome (DS) and associated with N-terminal truncating GATA1-mutations (GATA1s). Here we report that TL cell clones generate abundant eosinophils in a ...
    • High fat diet enhances stemness and tumorigenicity of intestinal progenitors 

      Beyaz, Semir; Mana, Miyeko D.; Roper, Jatin; Kedrin, Dmitriy; Saadatpour, Assieh; Hong, Sue-Jean; Bauer-Rowe, Khristian E.; Xifaras, Michael E.; Akkad, Adam; Arias, Erika; Pinello, Luca; Katz, Yarden; Shinagare, Shweta; Abu-Remaileh, Monther; Mihaylova, Maria M.; Lamming, Dudley W.; Dogum, Rizkullah; Guo, Guoji; Bell, George W.; Selig, Martin; Nielsen, G. Petur; Gupta, Nitin; Ferrone, Cristina R.; Deshpande, Vikram; Yuan, Guo-Cheng; Orkin, Stuart H.; Sabatini, David M.; Yilmaz, Ömer H. (2016)
      Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) ...
    • Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy 

      Stankov, Metodi V.; Khatib, Mona El; Thakur, Basant Kumar; Heitmann, Kirsten; Panayotova-Dimitrova, Diana; Schoening, Jennifer; Bourquin, Jean-Pierre; Schweitzer, Nora; Leverkus, Martin; Welte, Karl; Reinhardt, Dirk; Li, Zhe; Orkin, Stuart H.; Behrens, Georg M.N.; Klusmann, Jan-Henning (2014)
      Histone deacetylase (HDAC)-inhibitors (HDACis) are well characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant ...
    • Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation 

      Kerenyi, Marc A; Shao, Zhen; Hsu, Yu-Jung; Guo, Guoji; Luc, Sidinh; O'Brien, Kassandra; Fujiwara, Yuko; Peng, Cong; Nguyen, Minh; Orkin, Stuart H (eLife Sciences Publications, Ltd, 2013)
      Here, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic ...
    • Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis 

      Shimizu, Takafumi; Kubovcakova, Lucia; Nienhold, Ronny; Zmajkovic, Jakub; Meyer, Sara C.; Hao-Shen, Hui; Geier, Florian; Dirnhofer, Stephan; Guglielmelli, Paola; Vannucchi, Alessandro M.; Feenstra, Jelena D. Milosevic; Kralovics, Robert; Orkin, Stuart H.; Skoda, Radek C. (The Rockefeller University Press, 2016)
      Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic ...
    • LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice 

      Kim, Jeesun; Singh, Anup Kumar; Takata, Yoko; Lin, Kevin; Shen, Jianjun; Lu, Yue; Kerenyi, Marc A.; Orkin, Stuart H.; Chen, Taiping (Nature Publishing Group, 2015)
      Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by ...
    • The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability 

      Chung, Jacky; Bauer, Daniel Evan; Ghamari, Alireza; Nizzi, C. P.; Deck, K. M.; Kingsley, P. D.; Yien, Yvette Yee; Huston, N. C.; Chen, C.; Schultz, I. J.; Dalton, Arthur J.; Wittig, Johannes; Palis, J.; Orkin, Stuart Holland; Lodish, H. F.; Eisenstein, R. S.; Cantor, Alan B.; Paw, Barry Htin (American Association for the Advancement of Science (AAAS), 2015)
      In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral ...
    • Networking Erythropoiesis 

      Kerenyi, Marc; Orkin, Stuart Holland (The Rockefeller University Press, 2010)
      A relatively small cadre of lineage-restricted transcription factors largely orchestrates erythropoiesis, but how these nuclear factors interact to regulate this complex biology is still largely unknown. However, recent ...
    • Rb and Hematopoiesis: Stem Cells to Anemia 

      Walkley, Carl R; Sankaran, Vijay Ganesh; Orkin, Stuart Holland (BioMed Central, 2008)
      The retinoblastoma protein, Rb, was one of the first tumor suppressor genes identified as a result of the familial syndrome retinoblastoma. In the period since its identification and cloning a large number of studies have ...
    • Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence 

      Org, Tõnis; Duan, Dan; Ferrari, Roberto; Montel-Hagen, Amelie; Van Handel, Ben; Kerényi, Marc A; Sasidharan, Rajkumar; Rubbi, Liudmilla; Fujiwara, Yuko; Pellegrini, Matteo; Orkin, Stuart H; Kurdistani, Siavash K; Mikkola, Hanna KA (BlackWell Publishing Ltd, 2015)
      Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically ...
    • A Single cis Element Maintains Repression of the Key Developmental Regulator Gata2 

      Snow, Jonathan W.; Trowbridge, Jennifer J.; Fujiwara, Tohru; Emambokus, Nikla E.; Grass, Jeffrey A.; Orkin, Stuart Holland; Bresnick, Emery H. (Public Library of Science, 2010)
      In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are ...