Abstract
Stromal derived factor-1α (SDF-1α), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), was added to human CD34+ hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin-3 (IL-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14+ monocytic and CD41+ megakaryocytic lineages. While SDF-1α caused only modest effects on cells of the monocytic lineage, it induced profound down-regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF-1α initially up-regulated the early megakaryocytic antigen CD41, at later time points (days 12-16) it induced down-regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF-1α. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF-1α/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes. (C) 2000 Wiley-Liss, Inc.
| Original language | English |
|---|---|
| Pages (from-to) | 141-147 |
| Number of pages | 7 |
| Journal | Anatomical Record |
| Volume | 260 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 1 2000 |
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Keywords
- Bone marrow development
- Megakaryocytic cells
- SDF-1α
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Anatomy
Cite this
Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development. / Secchiero, Paola; Celeghini, Claudio; Cutroneo, Giuseppina; Di Baldassarre, Angela; Rana, Rosalba; Zauli, Giorgio.
In: Anatomical Record, Vol. 260, No. 2, 01.10.2000, p. 141-147.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development
AU - Secchiero, Paola
AU - Celeghini, Claudio
AU - Cutroneo, Giuseppina
AU - Di Baldassarre, Angela
AU - Rana, Rosalba
AU - Zauli, Giorgio
PY - 2000/10/1
Y1 - 2000/10/1
N2 - Stromal derived factor-1α (SDF-1α), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), was added to human CD34+ hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin-3 (IL-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14+ monocytic and CD41+ megakaryocytic lineages. While SDF-1α caused only modest effects on cells of the monocytic lineage, it induced profound down-regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF-1α initially up-regulated the early megakaryocytic antigen CD41, at later time points (days 12-16) it induced down-regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF-1α. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF-1α/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes. (C) 2000 Wiley-Liss, Inc.
AB - Stromal derived factor-1α (SDF-1α), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), was added to human CD34+ hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin-3 (IL-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14+ monocytic and CD41+ megakaryocytic lineages. While SDF-1α caused only modest effects on cells of the monocytic lineage, it induced profound down-regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF-1α initially up-regulated the early megakaryocytic antigen CD41, at later time points (days 12-16) it induced down-regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF-1α. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF-1α/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes. (C) 2000 Wiley-Liss, Inc.
KW - Bone marrow development
KW - Megakaryocytic cells
KW - SDF-1α
UR - http://www.scopus.com/inward/record.url?scp=0034307424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034307424&partnerID=8YFLogxK
U2 - 10.1002/1097-0185(20001001)260:2<141::AID-AR40>3.0.CO;2-I
DO - 10.1002/1097-0185(20001001)260:2<141::AID-AR40>3.0.CO;2-I
M3 - Article
C2 - 10993951
AN - SCOPUS:0034307424
VL - 260
SP - 141
EP - 147
JO - Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
JF - Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
SN - 0003-276X
IS - 2
ER -