PUA and C/EBPα/β convert fibroblasts into macrophage-like cells

被引:275
作者
Feng, Ru [2 ]
Desbordes, Sabrina C. [1 ]
Xie, Huafeng [2 ]
Tillo, Ester Sanchez [1 ]
Pixley, Fiona [2 ]
Stanley, E. Richard [2 ]
Graf, Thomas [1 ,2 ]
机构
[1] Ctr Genom Regulat, Differentiat & Canc Program, E-08003 Barcelona, Spain
[2] Albert Einstein Coll Med, Bronx, NY 10467 USA
关键词
cell reprogramming; differentiation plasticity; hematopoiesis;
D O I
10.1073/pnas.0711961105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Earlier work has shown that the transcription factor C/EBP alpha induced a transdifferentiation of committed lymphoid precursors into macrophages in a process requiring endogenous PU.1. Here we have examined the effects of PU.1 and C/EBP alpha on fibroblasts, a cell type distantly related to blood cells and akin to myoblasts, adipocytes, osteoblasts, and chondroblasts. The combination of the two factors, as well as PUA and C/EBP beta, induced the upregulation of macrophage/hematopoietic cell surface markers in a large proportion of NIH 3T3 cells. They also up-regulated these markers in mouse embryo- and adult skin-derived fibroblasts. Based on cell morphology, activation of macrophage-associated genes, and extinction of fibroblast-associated genes, cell lines containing an attenuated form of PU.1 and C/EBP alpha acquired a macrophage-like phenotype. The lines also display macrophage functions: They phagocytose small particles and bacteria, mount a partial inflammatory response, and exhibit strict CSF-1 dependence for growth. The myeloid conversion is primarily induced by PUA, with C/EBP alpha acting as a modulator of macrophage-specific gene expression. Our data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration.
引用
收藏
页码:6057 / 6062
页数:6
相关论文
共 29 条
  • [21] Transcriptional regulation in myelopoiesis: Hematopoietic fate choice, myeloid differentiation, and leukemogenesis
    Rosmarin, AG
    Yang, ZF
    Resendes, KK
    [J]. EXPERIMENTAL HEMATOLOGY, 2005, 33 (02) : 131 - 143
  • [22] A transcription factor party during blood cell differentiation
    Sieweke, MH
    Graf, T
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (05) : 545 - 551
  • [23] STANLEY ER, 1985, METHOD ENZYMOL, V116, P564
  • [24] Induction of pluripotent stem cells from adult human fibroblasts by defined factors
    Takahashi, Kazutoshi
    Tanabe, Koji
    Ohnuki, Mari
    Narita, Megumi
    Ichisaka, Tomoko
    Tomoda, Kiichiro
    Yamanaka, Shinya
    [J]. CELL, 2007, 131 (05) : 861 - 872
  • [25] ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages
    Tamura, T
    Nagamura-Inoue, T
    Shmeltzer, Z
    Kuwata, T
    Ozato, K
    [J]. IMMUNITY, 2000, 13 (02) : 155 - 165
  • [26] ACTIVATION OF MUSCLE-SPECIFIC GENES IN PIGMENT, NERVE, FAT, LIVER, AND FIBROBLAST CELL-LINES BY FORCED EXPRESSION OF MYOD
    WEINTRAUB, H
    TAPSCOTT, SJ
    DAVIS, RL
    THAYER, MJ
    ADAM, MA
    LASSAR, AB
    MILLER, AD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (14) : 5434 - 5438
  • [27] XIE H, 2004, CELL, V117, P1
  • [28] PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch
    Ye, M
    Ermakova, O
    Graf, T
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (10) : 1411 - 1422
  • [29] Role of PPARγ in macrophage biology and atherosclerosis
    Zhang, L
    Chawla, A
    [J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (10) : 500 - 505