RECENT PUBLICATIONS FROM THE LAB

Cell Stem Cell 2019 March 21. doi.org/10.1016/j.stem.2019.02.018

Puneet Agarwal, Stephan Isringhausen, Hui Li,  Andrew J. Paterson,  Jianbo He, A lvaro Gomariz,  Takashi Nagasawa, Cesar Nombela-Arrieta, and Ravi Bhatia

Leukemia. 2019 Jan 11. doi: 10.1038/s41375-018-0353-0

Lopez-Millan B, Sanchéz-Martínez D, Roca-Ho H, Gutiérrez-Agüera F, Molina O, Diaz de la Guardia R, Torres-Ruiz R, Fuster JL, Ballerini P, Suessbier U, Nombela-Arrieta C, Bueno C, Menéndez P.

QUANTITATIVE SPATIAL ANALYSIS OF HEMATOPOIESIS-REGULATING STROMAL CELLS IN THE BONE MAROW MICROENVIRONMENT BY 3D MICROSCOPY

Nat Commun. 2018 Jun 28;9(1):2532.

Sinusoidal endothelial cells and mesenchymal CXCL12-abundant reticular cells are principal bone marrow stromal components, which critically modulate haematopoiesis at various levels, including haematopoietic stem cell maintenance. These stromal subsets are thought to be scarce and function via highly specific interactions in anatomically confined niches. Yet, knowledge on their abundance, global distribution and spatial associations remains limited. Using three-dimensional quantitative microscopy we show that sinusoidal endothelial and mesenchymal reticular subsets are remarkably more abundant than estimated by conven- tional flow cytometry. Moreover, both cell types assemble in topologically complex networks, associate to extracellular matrix and pervade marrow tissues. Through spatial statistical methods we challenge previous models and demonstrate that even in the absence of major specific interaction forces, virtually all tissue-resident cells are invariably in physical contact with, or close proximity to, mesenchymal reticular and sinusoidal endothelial cells. We further show that basic structural features of these stromal components are preserved during ageing.

PATHOGEN-INDUCED TLR4-TRIF INNATE IMMUNE SIGNALING IN HEMATOPOIETIC STEM CELLS PROMOTES PROLIFERATION BUT REDUCES COMPETITIVE FITNESS

Cell Stem Cell. 2017 Aug 3;21(2):225-240.e5. doi: 10.1016/j.stem.2017.06.013

Takizawa H, Fritsch K, Kovtonyuk LV, Saito Y, Yakkala C, Jacobs K, Ahuja AK, Lopes M, Hausmann A, Hardt WD, Gomariz Á, Nombela-Arrieta C, Manz MG

J Immunol. 2017 Apr 1;198(7):2854-2864. doi: 10.4049/jimmunol.1602006

Zhu H, Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Kambara H, Yu H, Chai L, Silberstein LE, Cheng T, Luo HR

THE ROLE OF THE BONE MARROW STROMAL COMPARTMENT IN THE HEMATOPOIETIC RESPONSE TO MICROBIAL INFECTIONS.

Front Immunol. 2017 Jan 20;7:689. doi: 10.3389/fimmu.2016.00689

Nombela-Arrieta C, Isringhausen S.

G-CSF MAINTAINS CONTROLLED NEUTROPHIL MOBILIZATION DURING ACUTE INFLAMMATION BY NEGATIVELY REGULATING CXCR2 SIGNALING

J Exp Med. 2016 Sep 19;213(10):1999-2018. doi: 10.1084/jem.20160393

Bajrami B, Zhu H, Kwak HJ, Mondal S, Hou Q, Geng G, Karatepe K, Zhang YC, Nombela-Arrieta C, Park SY, Loison F, Sakai J, Xu Y, Silberstein LE, Luo HR.

MYELOID CELL-DERIVED REACTIVE OXYGEN SPECIES EXTERNALLY REGULATE THE PROLIFERATION OF MYELOID PROGENITORS IN EMERGENCY GRANULOPOIESIS.

Immunity. 2015 Jan 20;42(1):159-71. doi: 10.1016/j.immuni.2014.12.017.

Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Sun Y, Zhu H, Chai L, Silberstein LE, Cheng T, Luo HR.

Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):542-7. doi: 10.1182/asheducation-2014.1.54

Nombela-Arrieta C, Silberstein LE.

FGD5 IDENTIFIES HEMATOPOIETIC STEM CELLS IN THE MURINE BONE MARROW

J Exp Med. 2014 Jun 30;211(7):1315-31. doi: 10.1084/jem.20130428

  

Gazit R, Mandal PK, Ebina W, Ben-Zvi A, Nombela-Arrieta C, Silberstein LE, Rossi DJ.

DEFICIENCY OF LIPID PHOSPHATASE SHIP ENABLES LONG-TERM RECONSTITUTION OF HEMATOPOIETIC INDUCTIVE BONE MARROW MICROENVIRONMENT

Dev Cell. 2013 May 28;25(4):333-49. doi: 10.1016/j.devcel.2013.04.016.

Liang OD, Lu J, Nombela-Arrieta C, Zhong J, Zhao L, Pivarnik G, Mondal S, Chai L, Silberstein LE, Luo HR.

RHYTHMIC MODULATION OF THE HEMATOPOIETIC NICHE THROUGH NEUTROPHIL CLEARANCE.

Cell. 2013 May 23;153(5):1025-35. doi: 10.1016/j.cell.2013.04.040.

Casanova-Acebes M, Pitaval C, Weiss LA, Nombela-Arrieta C, Chèvre R, A-González N, Kunisaki Y, Zhang D, van Rooijen N, Silberstein LE, Weber C, Nagasawa T, Frenette PS, Castrillo A, Hidalgo A.

QUANTITATIVE IMAGING OF HAEMATOPOIETIC STEM AND PROGENITOR CELL LOCALIZATION AND HYPOXIC STATUS IN THE BONE MARROW MICROENVIRONMENT

Nat Cell Biol. 2013 May;15(5):533-43. doi: 10.1038/ncb2730

Nombela-Arrieta C*, Pivarnik G, Winkel B, Canty KJ, Harley B, Mahoney JE, Park SY, Lu J, Protopopov A, Silberstein LE*.

*co-corresponding author

SUSTAINED PU.1 LEVELS BALANCE CELL-CYCLE REGULATORS TO PREVENT EXHAUSTION OF ADULT HEMATOPOIETIC STEM CELLS

Mol Cell. 2013 Mar 7;49(5):934-46. doi: 10.1016/j.molcel.2013.01.007

Staber PB, Zhang P, Ye M, Welner RS, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jordà M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Orkin SH, Göttgens B, Rosenbauer F, Huang G, Tenen DG.

FOCAL ADHESION KINASE REGULATES THE LOCALIZATION AND RETENTION OF PRO-B CELLS IN BONE MARROW MICROENVIRONMENTS

J Immunol. 2013 Feb 1;190(3):1094-102. doi: 10.4049/jimmunol.1202639

Park SY, Wolfram P, Canty K, Harley B, Nombela-Arrieta C, Pivarnik G, Manis J, Beggs HE, Silberstein LE

IN VIVO GENERATION OF TRANSPLANTABLE HUMAN HEMATOPOIETIC CELLS FROM INDUCED PLURIPOTENT STEM CELLS

Blood. 2013 Feb 21;121(8):1255-64. doi: 10.1182/blood-2012-06-434407

Amabile G, Welner RS, Nombela-Arrieta C, D'Alise AM, Di Ruscio A, Ebralidze AK, Kraytsberg Y, Ye M, Kocher O, Neuberg DS, Khrapko K, Silberstein LE, Tenen DG

FAK DEPLETION IN BOTH HEMATOPOIETIC AND NONHEMATOPOIETIC NICHE CELLS LEADS TO HEMATOPOIETIC STEM CELL EXPANSION

Exp Hematol. 2012 Apr;40(4):307-17.e3. doi: 10.1016/j.exphem.2011.11.010

Lu J, Sun Y, Nombela-Arrieta C, Du KP, Park SY, Chai L, Walkley C, Luo HR, Silberstein LE

THE ELUSIVE NATURE AND FUNCTION OF MESENCHYMAL STEM CELLS

Nat Rev Mol Cell Biol. 2011 Feb;12(2):126-31. doi: 10.1038/nrm3049. Review

Nombela-Arrieta C, Ritz J, Silberstein LE

A CENTRAL ROLE FOR DOCK2 DURING INTERSTITIAL LYMPHOCYTE MOTILITY AND SPHINGOSINE-1-PHOSPHATE-MEDIATED EGRESS

J Exp Med. 2007 Mar 19;204(3):497-510.

Nombela-Arrieta C, Mempel TR, Soriano SF, Mazo I, Wymann MP, Hirsch E, Martínez-A C, Fukui Y, von Andrian UH, Stein JV

DOCK2 IS REQUIRED FOR CHEMOKINE-PROMOTED HUMAN T LYMPHOCYTE ADHESION UNDER SHEAR STRESS MEDIATED BY THE INTEGRIN ALPHA4BETA1

J Immunol. 2006 Oct 15;177(8):5215-25.

García-Bernal D, Sotillo-Mallo E, Nombela-Arrieta C, Samaniego R, Fukui Y, Stein JV, Teixidó J.

CHEMOKINE CONTROL OF LYMPHOCYTE TRAFFICKING: A GENERAL OVERVIEW

Immunology. 2005 Sep;116(1):1-12. Review.

Stein JV, Nombela-Arrieta C

VAV1 AND RAC CONTROL CHEMOKINE-PROMOTED T LYMPHOCYTE ADHESION MEDIATED BY THE INTEGRIN ALPHA4BETA1.

Mol Biol Cell. 2005 Jul;16(7):3223-35

García-Bernal D, Wright N, Sotillo-Mallo E, Nombela-Arrieta C, Stein JV, Bustelo XR, Teixidó J

CCR7-MEDIATED PHYSIOLOGICAL LYMPHOCYTE HOMING INVOLVES ACTIVATION OF A TYROSINE KINASE PATHWAY

Blood. 2003 Jan 1;101(1):38-44.

Stein JV, Soriano SF, M'rini C, Nombela-Arrieta C, de Buitrago GG, Rodríguez-Frade JM, Mellado M, Girard JP, Martínez-A C.

DIFFERENTIAL REQUIREMENTS FOR DOCK2 AND PHOSPHOINOSITIDE-3-KINASE GAMMA DURING T AND B LYMPHOCYTE HOMING

Immunity. 2004 Sep;21(3):429-41.

Nombela-Arrieta C, Lacalle RA, Montoya MC, Kunisaki Y, Megías D, Marqués M, Carrera AC, Mañes S, Fukui Y, Martínez-A C, Stein JV.

QUANTIFICATION AND THREE-DIMENSIONAL MICROANATOMICAL ORGANIZATION OF THE BONE MARROW

January 2017

Bone marrow (BM) constitutes one of the largest organs in mice and humans, continuously generating, in a highly regulated manner, red blood cells, platelets, and white blood cells that together form the majority of cells of the body. In this review, we provide a quantitative overview of BM cellular composition, we summarize emerging knowledge on its structural organization and cellular niches, and we argue for the need of multidimensional approaches such as recently developed imaging techniques to uncover the complex spatial logic that underlies BM function in health and disease