Antagonistic Regulation by the Transcription Factors C/EBP alpha and MITF Specifies Basophil and Mast Cell Fates

作者：Qi Xiaopeng; Hong Jessie; Chaves Lee; Zhuang Yonghua; Chen Yuhong; Wang Demin; Chabon Jacob; Graham Brian; Ohmori Keitaro; Li Yapeng; Huang Hua^*

来源：Immunity, 2013, 39(1): 97-110.

DOI：10.1016/j.immuni.2013.06.012

It remains unclear whether basophils and mast cells are derived from a common progenitor. Furthermore, how basophil versus mast cell fate is specified has not been investigated. Here, we have identified a population of granulocyte-macrophage progenitors (GMPs) that were highly enriched in the capacity to differentiate into basophils and mast cells while retaining a limited capacity to differentiate into myeloid cells. We have designated these progenitor cells "pre-basophil and mast cell progenitors" (preBMPs). STAT5 signaling was required for the differentiation of pre-BMPs into both basophils and mast cells and was critical for inducing two downstream molecules: C/EBP alpha and MITF. We have identified C/EBP alpha as the critical basophil transcription factor for specifying basophil cell fate and MITF as the crucial transcription factor for specifying mast cell fate. C/EBP alpha and MITF silenced each other's transcription in a directly antagonistic fashion. Our study reveals how basophil and mast cell fate is specified.

• 出版日期2013-7-25