PU.1 is required for the Developmental Progression of Multipotent Progenitors to common lymphoid Progenitors

被引：29

作者：

Pang, Swee Heng Milon ^{[1
,2
]}

de Graaf, Carolyn A. ^{[1
,2
]}

Hilton, Douglas J. ^{[1
,2
]}

Huntington, Nicholas D. ^{[1
,2
]}

Carotta, Sebastian ^{[1
,2
,3
]}

Wu, Li ^{[1
,2
,4
]}

Nutt, Stephen L. ^{[1
,2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia

[3] Boehringer Ingelheim GmbH & Co KG, Oncol Res, Vienna, Austria

[4] Tsinghua Univ, Inst Immunol, Sch Med, Beijing, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

PU.1; transcription factor; multipotent progenitor; common lymphoid progenitor; Rag1; B-CELL-DEVELOPMENT; TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; LINEAGE COMMITMENT; INTERLEUKIN-7; RECEPTOR; REGULATORY NETWORK; ENCODING PU.1; FATE CHOICE; RAG1; LOCUS; EXPRESSION;

D O I：

10.3389/fimmu.2018.01264

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The transcription factor PU.1 is required for the development of mature myeloid and lymphoid cells. Due to this essential role and the importance of PU.1 in regulating several signature markers of lymphoid progenitors, its precise function in early lymphopoiesis has been difficult to define. Here, we demonstrate that PU.1 was required for efficient generation of lymphoid-primed multipotent progenitors (LMPPs) from hematopoietic stem cells and was essential for the subsequent formation of common lymphoid progenitors (CLPs). By contrast, further differentiation into the B-cell lineage was independent of PU.1. Examination of the transcriptional changes in conditional progenitors revealed that PU.1 activates lymphoid genes in LMPPs, while repressing genes normally expressed in neutrophils. These data identify PU.1 as a critical regulator of lymphoid priming and the transition between LMPPs and CLPs.

引用

页数：11

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