Quiescence of CD34-negative haematopoietic stem cells is mediated by downregulation of Cyclin B and no stat activation

TY - JOUR

T1 - Quiescence of CD34-negative haematopoietic stem cells is mediated by downregulation of Cyclin B and no stat activation

AU - Huss, R

AU - Gatsios, P

AU - Graeve, L

AU - Lange, Claudia

AU - Eissner, G

AU - Kolb, H J

AU - Thalmeier, K

AU - Heinrich, P C

N1 - Copyright 2000 Academic Press.

PY - 2000/8/1

Y1 - 2000/8/1

N2 - The CD34-negative, adherent growing, fibroblast-like canine haematopoietic stem cell line D064 was recently identified as the earliest progenitor population in the bone marrow. D064 cells are predominately quiescent. Quiescence is mediated by the accumulation of the cyclin-dependent kinase inhibitor p27(kip-1)and in parallel, by the downregulation of Cyclin B, leading to an accumulation of quiescent cells in the G(0)/G(1)-phase of the cell cycle. Stem cell factor (SCF), the ligand for the tyrosine kinase receptor c-kit, usually induces differentiation of the CD34-negative stem cells into CD34-positive haematopoietic precursors. SCF also suppresses the expression of c-myc-dependent Cyclin E, which is not transcribed initially, but expression occurs later on. Interleukin 6 (IL-6) instead rather promotes proliferation, but fails to induce proliferation in the majority of CD34-negative stem cells due to no STAT activation in quiescent cells. Nevertheless, the potential of quiescent D064 cells to proliferate eventually, becomes apparent by the low-level expression of IL-6 dependent STAT factors. D064 cells also spontaneously start to express Bax, while Bcl-2 is downregulated in parallel. In summary, CD34-negative haematopoietic stem cells dwell in the marrow or other niches as quiescent cells, until they can respond to autocrine or paracrine growth factor-mediated signals.

AB - The CD34-negative, adherent growing, fibroblast-like canine haematopoietic stem cell line D064 was recently identified as the earliest progenitor population in the bone marrow. D064 cells are predominately quiescent. Quiescence is mediated by the accumulation of the cyclin-dependent kinase inhibitor p27(kip-1)and in parallel, by the downregulation of Cyclin B, leading to an accumulation of quiescent cells in the G(0)/G(1)-phase of the cell cycle. Stem cell factor (SCF), the ligand for the tyrosine kinase receptor c-kit, usually induces differentiation of the CD34-negative stem cells into CD34-positive haematopoietic precursors. SCF also suppresses the expression of c-myc-dependent Cyclin E, which is not transcribed initially, but expression occurs later on. Interleukin 6 (IL-6) instead rather promotes proliferation, but fails to induce proliferation in the majority of CD34-negative stem cells due to no STAT activation in quiescent cells. Nevertheless, the potential of quiescent D064 cells to proliferate eventually, becomes apparent by the low-level expression of IL-6 dependent STAT factors. D064 cells also spontaneously start to express Bax, while Bcl-2 is downregulated in parallel. In summary, CD34-negative haematopoietic stem cells dwell in the marrow or other niches as quiescent cells, until they can respond to autocrine or paracrine growth factor-mediated signals.

KW - Animals

KW - Antigens, CD34

KW - COS Cells

KW - Cell Cycle

KW - Cell Cycle Proteins

KW - Cell Division

KW - Cells, Cultured

KW - Cyclin B

KW - DNA-Binding Proteins

KW - Dogs

KW - Down-Regulation

KW - Hematopoietic Stem Cells

KW - Humans

KW - Interleukin-6

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-bcl-2

KW - Proto-Oncogene Proteins c-myc

KW - STAT1 Transcription Factor

KW - Stem Cell Factor

KW - Trans-Activators

KW - Transcription, Genetic

KW - bcl-2-Associated X Protein

U2 - 10.1006/cyto.1999.0732

DO - 10.1006/cyto.1999.0732

M3 - SCORING: Journal article

C2 - 10930296

VL - 12

SP - 1195

EP - 1204

JO - CYTOKINE

JF - CYTOKINE

SN - 1043-4666

IS - 8

ER -