LYMPHOHEMATOPOIETIC PROGENITORS IMMORTALIZED BY A RETROVIRAL VECTOR HARBORING A DOMINANT-NEGATIVE RETINOIC ACID RECEPTOR CAN RECAPITULATE LYMPHOID, MYELOID, AND ERYTHROID DEVELOPMENT

被引:240
作者
TSAI, S [1 ]
BARTELMEZ, S [1 ]
SITNICKA, E [1 ]
COLLINS, S [1 ]
机构
[1] UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195
关键词
RETINOIC ACID RECEPTORS; LYMPHOHEMATOPOIETIC PROGENITORS; B-CELL DEVELOPMENT; MYELOPOIESIS; ERYTHROPOIESIS;
D O I
10.1101/gad.8.23.2831
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The lymphohematopoietic progenitors represent <0.01% of nucleated marrow cells. Here, we describe the immortalization of the murine lymphohematopoietic progenitors by a retroviral vector harboring a dominant-negative retinoic acid receptor. The immortalized progenitors proliferate as a stem-cell-factor-dependent clonal line EML that spontaneously generates pre-pro-B lymphocytes and erythroid and myeloid progenitors. Upon stimulation with interleukin-7 and stromal cells, the pre-pro-B lymphocytes express RAG-1 and undergo D-J rearrangements of the immunoglobulin heavy-chain genes. With erythropoietin the erythroid progenitors proliferate and differentiate into red cells. Generation of the common progenitors for neutrophils and macrophages is suppressed in EML but is inducible by high concentrations of retinoic acid. An additional block in neutrophil differentiation occurs at the promyelocyte stage but can also be overcome by high concentrations of retinoic acid. These studies demonstrate a reproducible way to immortalize lymphohematopoietic progenitors and implicate specific roles for retinoic acid receptors at two distinct stages of hematopoiesis.
引用
收藏
页码:2831 / 2841
页数:11
相关论文
共 36 条
  • [1] TRANSLOCATION BREAKPOINT OF ACUTE PROMYELOCYTIC LEUKEMIA LIES WITHIN THE RETINOIC ACID RECEPTOR-ALPHA LOCUS
    ALCALAY, M
    ZANGRILLI, D
    PANDOLFI, PP
    LONGO, L
    MENCARELLI, A
    GIACOMUCCI, A
    ROCCHI, M
    BIONDI, A
    RAMBALDI, A
    LOCOCO, F
    DIVERIO, D
    DONTI, E
    GRIGNANI, F
    PELICCI, PG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (05) : 1977 - 1981
  • [2] DEVELOPMENT OF THE PRIMARY ANTIBODY REPERTOIRE
    ALT, FW
    BLACKWELL, TK
    YANCOPOULOS, GD
    [J]. SCIENCE, 1987, 238 (4830) : 1079 - 1087
  • [3] MOLECULAR ANALYSIS OF ACUTE PROMYELOCYTIC LEUKEMIA BREAKPOINT CLUSTER REGION ON CHROMOSOME-17
    BORROW, J
    GODDARD, AD
    SHEER, D
    SOLOMON, E
    [J]. SCIENCE, 1990, 249 (4976) : 1577 - 1580
  • [4] INDUCTION OF DIFFERENTIATION OF THE HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE (HL-60) BY RETINOIC ACID
    BREITMAN, TR
    SELONICK, SE
    COLLINS, SJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (05): : 2936 - 2940
  • [5] B220 - A B-CELL-SPECIFIC MEMBER OF THE T200 GLYCOPROTEIN FAMILY
    COFFMAN, RL
    WEISSMAN, IL
    [J]. NATURE, 1981, 289 (5799) : 681 - 683
  • [6] RETINOIC ACID-INDUCED GRANULOCYTIC DIFFERENTIATION OF HL-60 MYELOID-LEUKEMIA CELLS IS MEDIATED DIRECTLY THROUGH THE RETINOIC ACID RECEPTOR (RAR-ALPHA)
    COLLINS, SJ
    ROBERTSON, KA
    MUELLER, L
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (05) : 2154 - 2163
  • [7] DAMM K, 1993, P NATL ACAD SCI USA, V90, P1989
  • [8] RETINOIC ACID - ENDOGENOUS COMPOUND OF HUMAN-BLOOD - UNEQUIVOCAL DEMONSTRATION OF ENDOGENOUS RETINOIC ACID IN NORMAL PHYSIOLOGICAL CONDITIONS
    DERUYTER, MG
    LAMBERT, WE
    DELEENHEER, AP
    [J]. ANALYTICAL BIOCHEMISTRY, 1979, 98 (02) : 402 - 409
  • [9] THE PML-RAR-ALPHA FUSION MESSENGER-RNA GENERATED BY THE T(15-17) TRANSLOCATION IN ACUTE PROMYELOCYTIC LEUKEMIA ENCODES A FUNCTIONALLY ALTERED RAR
    DETHE, H
    LAVAU, C
    MARCHIO, A
    CHOMIENNE, C
    DEGOS, L
    DEJEAN, A
    [J]. CELL, 1991, 66 (04) : 675 - 684
  • [10] THE T(15-17) TRANSLOCATION OF ACUTE PROMYELOCYTIC LEUKEMIA FUSES THE RETINOIC ACID RECEPTOR-ALPHA GENE TO A NOVEL TRANSCRIBED LOCUS
    DETHE, H
    CHOMIENNE, C
    LANOTTE, M
    DEGOS, L
    DEJEAN, A
    [J]. NATURE, 1990, 347 (6293) : 558 - 561