Differential effects of transforming growth factor-β1 on distinct developmental stages of murine meeakaryocytopoiesis

Heather Jackson, Neil Williams, Keith R. Westcott, Ralph Green

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The effect of transforming growth factor-β1 (TGFβ1) on three developmental stages of megakaryocytopoiesis was investigated. Using a murine bone marrow agar culture system, titrated doses of TGFβ1 were added to cultures assaying primitive high proliferative megakaryocyte progenitors, committed megakaryocyte precursors, and nondividing, endoreduplicating megakaryocytes. The growth of high proliferative megakaryocyte colony-forming cells (HPP-CFU-Mk) that require the growth factors interleukins-1, 3 and 6 (IL-1 + IL-3 + IL-6) for colony detection was abrogated by the addition of 1 ng TGFβ1/ml. The sensitivity of committed megakaryocyte progenitors (colony-forming unit-megakaryocyte, CFU-Mk) to TGFβ1 depended on the growth factor combination. TGFβ1 (1 ng/ml) completely inhibited megakaryocyte colony formation from CFU-Mk only in cultures stimulated by low doses of IL-3. TGFβ1 (>10 ng/ml) could only marginally inhibit megakaryocyte colony formation generated in the presence of either high doses of IL-3 or the combination of low dose IL-3 + IL-6. TGFβ1 inhibited both IL-3-dependent and IL-6-dependent megakaryocyte growth but tenfold higher doses of TGFβ1 were required to inhibit growth generated by the combination of IL-3 + IL-6. The data showed that the capacity of TGFβ1 to inhibit distinct differentiation stages of the megakaryocytopoietic lineage depended on the concentration and combination of growth factors involved.

Original languageEnglish (US)
Pages (from-to)312-318
Number of pages7
JournalJournal of Cellular Physiology
Volume161
Issue number2
StatePublished - Nov 1994
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

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