Cell cycle entry of hematopoietic stem and progenitor cells controlled by distinct cyclin-dependent kinase inhibitors

被引:32
作者
Cheng, T
Scadden, DT
机构
[1] Univ Pittsburgh, Canc Inst, Sch Med, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Radiat Oncol, Sch Med, Pittsburgh, PA 15213 USA
[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA
[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA USA
关键词
hematopoietic stem cells; cell cycle; p21; p27; TGF-beta; 1;
D O I
10.1007/BF02982107
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The therapeutic promise of hematopoietic stem cells in medicine has been expanded as broader differentiation potential of the cells has gained experimental support. However, hurdles for stem cell manipulation in vitro and tissue regeneration in vivo remain because of lack of the molecular biology of the stem cells. In particular, elucidating the molecular control of cell cycle entry is necessary for rational stem cell expansion strategies. Understanding how the stem and progenitor cell populations are controlled by negative regulators of cell cycle entry may provide one basis for manipulating these cells. In this mini-review, we focus on the rationale of targeting the cyclin-dependent kinase inhibitors (CKIs) in stem cell biology. Two CKI members, p21(Cip1/Waf1) (p21) and p27(kip1) (p27), have been shown to govern the pool sizes of hematopoietic stem and progenitor cells, respectively. Of note, their inhibitory roles in primitive hematopoietic cells are distinct from the action of the inhibitory cytokine, transforming growth factor-beta1 (TGF-beta1). Therefore, the distinct roles of p21, p27, and TGF-beta1 in hematopoietic cells offer attractive targets for specific manipulation of the stem or progenitor cell populations in therapeutic strategies. (C) 2002 The Japanese Society of Hematology.
引用
收藏
页码:460 / 465
页数:6
相关论文
共 85 条
  • [1] Evidence that hematopoiesis may be a stochastic process in vivo
    Abkowitz, JL
    Catlin, SN
    Guttorp, P
    [J]. NATURE MEDICINE, 1996, 2 (02) : 190 - 197
  • [2] Adhesion receptor expression by hematopoietic cell lines and murine progenitors: Modulation by cytokines and cell cycle status
    Becker, PS
    Nilsson, SK
    Li, ZF
    Berrios, VM
    Dooner, MS
    Cooper, CL
    Hsieh, CC
    Quesenberry, PJ
    [J]. EXPERIMENTAL HEMATOLOGY, 1999, 27 (03) : 533 - 541
  • [3] FUNCTIONAL ISOLATION AND CHARACTERIZATION OF HUMAN HEMATOPOIETIC STEM-CELLS
    BERARDI, AC
    WANG, AL
    LEVINE, JD
    LOPEZ, P
    SCADDEN, DT
    [J]. SCIENCE, 1995, 267 (5194) : 104 - 108
  • [4] Bradford GB, 1997, EXP HEMATOL, V25, P445
  • [5] A positive effect of p21cip1/waf1 in the colony formation from murine myeloid progenitor cells as assessed by retroviral-mediated gene transfer
    Braun, SE
    Mantel, C
    Rosenthal, M
    Cooper, S
    Liu, L
    Robertson, KA
    Hromas, R
    Broxmeyer, HE
    [J]. BLOOD CELLS MOLECULES AND DISEASES, 1998, 24 (08) : 138 - 148
  • [6] BROXMEYER HE, 1990, BLOOD, V76, P1110
  • [7] RADIATION-INDUCED CELL-CYCLE ARREST COMPROMISED BY P21 DEFICIENCY
    BRUGAROLAS, J
    CHANDRASEKARAN, C
    GORDON, JI
    BEACH, D
    JACKS, T
    HANNON, GJ
    [J]. NATURE, 1995, 377 (6549) : 552 - 557
  • [8] RELEASE FROM QUIESCENCE OF CD34+ CD38- HUMAN UMBILICAL-CORD BLOOD-CELLS REVEALS THEIR POTENTIALITY TO ENGRAFT ADULTS
    CARDOSO, AA
    LI, ML
    BATARD, P
    HATZFELD, A
    BROWN, EL
    LEVESQUE, JP
    SOOKDEO, H
    PANTERNE, B
    SANSILVESTRI, P
    CLARK, SC
    HATZFELD, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (18) : 8707 - 8711
  • [9] Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model
    Cashman, JD
    Clark-Lewis, I
    Eaves, AC
    Eaves, CJ
    [J]. BLOOD, 1999, 94 (11) : 3722 - 3729
  • [10] The p21Cip1 and p27Kip1 CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts
    Cheng, MG
    Olivier, P
    Diehl, JA
    Fero, M
    Roussel, MF
    Roberts, JM
    Sherr, CJ
    [J]. EMBO JOURNAL, 1999, 18 (06) : 1571 - 1583