Monocytically differentiating HL60 cells proliferate rapidly before they mature

Geoffrey Brown, M. Ansar Choudhry, Jennifer Durham, Mark T. Drayson, Robert H. Michell

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

1α,25-Dihydroxyvitamin D3 (D3) provokes growth arrest and monocytic differentiation in myeloid cells. Although it is usually assumed that the cellular events leading to growth arrest start within one cell cycle of D3 addition, there is also evidence that D3 provokes the expression of proliferation-related genes and accelerates cell division. Herein we clarify the relationship between proliferation and maturation in differentiating HL60 cells. Cells were cultured singly, D3 was added at various stages of the cell cycle, the progeny were counted, and the proportions of mature monocytes were determined. Initially, the D3-treated cells proliferated at an accelerated rate, and they matured only later. If cells encountered D3 early in G1 they divided two to four times before maturing, and if they encountered D3 later in the cell cycle they underwent an extra division. Indomethacin slows HL60 cell multiplication by prolonging G1, and when these slower- growing cells were exposed to D3, they matured after the usual period but underwent one division less than indomethacin-free cells. Contrary to common assumptions, we conclude that promyeloid cells do not initiate growth arrest or monocytic maturation immediately after exposure to D3. Instead, an encounter with D3 early in G1 sets in train a complex differentiation program. This consists of 2-3 days of rapid proliferation - probably employing cell cycles with a shortened G1 phase - that is followed by growth arrest and maturation. As a result, a single D3-treated promyeloid cell gives rise to 10 or more mature monocytes. These observations not only explain why 'differentiating' cells express proliferation-related characteristics soon after D3 addition, but they also show that the process of D3-induced monocytic differentiation is much more complex than has previously been realized.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalExperimental Cell Research
Volume253
Issue number2
DOIs
Publication statusPublished - 15 Dec 1999

Keywords

  • HL-60 cells
  • Myeloid cell differentiation
  • Myeloid cell proliferation
  • Vitamin D

ASJC Scopus subject areas

  • Cell Biology

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