Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation

Abstract

A Different Cycle for Differentiation The regulated expression of transcription factors determines cell fate decisions during cell differentiation. The transcription factor PU.1 is an important determinant in the differentiation of hematopoietic progenitors to lymphocytes or myeloid cells, where high expression induces macrophage differentiation, whereas low expression leads to the development of B lymphocytes. How PU.1 expression levels are regulated during this cell fate choice, however, is not well understood. Kueh et al. (p. 670 , published online 18 July) found that in mice, reduced transcription of PU.1 led to its reduced expression in developing B lymphocytes, whereas in macrophages, PU.1 was able to accumulate stably because of a lengthening of the cell cycle. Exogenous expression of PU.1 in progenitors supported cell cycle lengthening and macrophage differentiation, and mathematical modeling suggested that such a feedback loop could maintain a slow-dividing macrophage developmental state.