The role of Smad signaling in hematopoiesis and translational hematology

被引:97
作者
Blank, U. [1 ]
Karlsson, S. [1 ]
机构
[1] Univ Lund Hosp, Div Mol Med & Gene Therapy, Lab Med, Lund Stem Cell Ctr, S-22184 Lund, Sweden
基金
英国医学研究理事会;
关键词
hematopoietic stem cell; smad signaling; TGF-beta; GROWTH-FACTOR-BETA; EX-VIVO EXPANSION; BONE MORPHOGENETIC PROTEIN-4; EMBRYONIC STEM-CELLS; RECEPTOR-TYPE-II; TGF-BETA; SELF-RENEWAL; TRANSFORMING GROWTH-FACTOR-BETA-1; PROGENITOR CELLS; IN-VIVO;
D O I
10.1038/leu.2011.95
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) of adult individuals and function to produce and regenerate the entire blood and immune system over the course of an individual's lifetime. Historically, HSCs are among the most thoroughly characterized tissue-specific stem cells. Despite this, the regulation of fate options, such as self-renewal and differentiation, has remained elusive, partly because of the expansive plethora of factors and signaling cues that govern HSC behavior in vivo. In the BM, HSCs are housed in specialized niches that dovetail the behavior of HSCs with the need of the organism. The Smad-signaling pathway, which operates downstream of the transforming growth factor-beta (TGF-beta) superfamily of ligands, regulates a diverse set of biological processes, including proliferation, differentiation and apoptosis, in many different organ systems. Much of the function of Smad signaling in hematopoiesis has remained nebulous due to early embryonic lethality of most knockout mouse models. However, recently new data have been uncovered, suggesting that the Smad-signaling circuitry is intimately linked to HSC regulation. In this review, we bring the Smad-signaling pathway into focus, chronicling key concepts and recent advances with respect to TGF-beta-superfamily signaling in normal and leukemic hematopoiesis. Leukemia (2011) 25, 1379-1388; doi: 10.1038/leu.2011.95; published online 13 May 2011
引用
收藏
页码:1379 / 1388
页数:10
相关论文
共 131 条
  • [1] HOXB4-induced expansion of adult hematopoietic stem cells ex vivo
    Antonchuk, J
    Sauvageau, G
    Humphries, RK
    [J]. CELL, 2002, 109 (01) : 39 - 45
  • [2] Regulation of hematopoietic stem cell growth
    Attar, EC
    Scadden, DT
    [J]. LEUKEMIA, 2004, 18 (11) : 1760 - 1768
  • [3] TIF1γ Controls Erythroid Cell Fate by Regulating Transcription Elongation
    Bai, Xiaoying
    Kim, Jonghwan
    Yang, Zhongan
    Jurynec, Michael J.
    Akie, Thomas E.
    Lee, Joseph
    LeBlanc, Jocelyn
    Sessa, Anna
    Jiang, Hong
    DiBiase, Anthony
    Zhou, Yi
    Grunwald, David J.
    Lin, Shuo
    Cantor, Alan B.
    Orkin, Stuart H.
    Zon, Leonard I.
    [J]. CELL, 2010, 142 (01) : 133 - 143
  • [4] Batard P, 2000, J CELL SCI, V113, P383
  • [5] Side effects of retroviral gene transfer into hematopoietic stem cells
    Baum, C
    Düllmann, J
    Li, ZX
    Fehse, B
    Meyer, J
    Williams, DA
    von Kalle, C
    [J]. BLOOD, 2003, 101 (06) : 2099 - 2114
  • [6] Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation
    Bhardwaj, G
    Murdoch, B
    Wu, D
    Baker, DP
    Williams, KP
    Chadwick, K
    Ling, LE
    Karanu, FN
    Bhatia, M
    [J]. NATURE IMMUNOLOGY, 2001, 2 (02) : 172 - 180
  • [7] Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells
    Bhatia, M
    Bonnet, D
    Wu, DM
    Murdoch, B
    Wrana, J
    Gallacher, L
    Dick, JE
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (07) : 1139 - 1147
  • [8] Smad7 promotes self-renewal of hematopoietic stem cells
    Blank, Ulrika
    Karlsson, Goran
    Moody, Jennifer L.
    Utsugisawa, Taiju
    Magnusson, Mattias
    Singbrant, Sofie
    Larsson, Jonas
    Karlsson, Stefan
    [J]. BLOOD, 2006, 108 (13) : 4246 - 4254
  • [9] BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism
    Blank, Ulrika
    Brown, Aaron
    Adams, Derek C.
    Karolak, Michele J.
    Oxburgh, Leif
    [J]. DEVELOPMENT, 2009, 136 (21): : 3557 - 3566
  • [10] Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells
    Boitano, Anthony E.
    Wang, Jian
    Romeo, Russell
    Bouchez, Laure C.
    Parker, Albert E.
    Sutton, Sue E.
    Walker, John R.
    Flaveny, Colin A.
    Perdew, Gary H.
    Denison, Michael S.
    Schultz, Peter G.
    Cooke, Michael P.
    [J]. SCIENCE, 2010, 329 (5997) : 1345 - 1348