Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development

Paola Secchiero, Claudio Celeghini, Giuseppina Cutroneo, Angela Di Baldassarre, Rosalba Rana, Giorgio Zauli

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)141-147
Number of pages7
JournalAnatomical Record
Volume260
Issue number2
DOIs
Publication statusPublished - Oct 1 2000

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CXCR4 Receptors
human development
Human Development
stem cell factor
megakaryocytes
antigen
Stem Cell Factor
Megakaryocytes
Down-Regulation
Megakaryocyte Progenitor Cells
macrophage colony-stimulating factor
Platelet Glycoprotein GPIb-IX Complex
interleukin-3
Platelet Membrane Glycoprotein IIb
antigens
Thrombopoietin
ligand
Macrophage Colony-Stimulating Factor
serum
Interleukin-3

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 journalArticle

Secchiero, Paola ; Celeghini, Claudio ; Cutroneo, Giuseppina ; Di Baldassarre, Angela ; Rana, Rosalba ; Zauli, Giorgio. / Differential effects of stromal derived factor-1α (SDF-1α) on early and late stages of human megakaryocytic development. In: Anatomical Record. 2000 ; Vol. 260, No. 2. pp. 141-147.
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AU - Rana, Rosalba

AU - Zauli, Giorgio

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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.

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