Th-POK: Metabolic regulator beyond cell fate determination

A team of researchers at Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences, reported Feb 8 online in PLOS Genetics, identified Th-POK as an important metabolic regulator of mammary gland lactation.

 

ZHANG Rui, MA Huimin, GAO Yuan and their colleagues, supervised by Dr. GE Gaoxiang and Dr. LIU Xiaolong from SIBCB, discovered Th-POK is essential to the proper functions of mammary glands, in particular the onset of lactation upon parturition.

 

Transition from pregnancy to lactation upon parturition, a process known as secretory activation, is a critical event in producing sufficient milk and nutrients to the infants. Such a process, however, is not well understood.

 

Th-POK, aka cKrox or ZBTB7B, is a zinc finger transcription factor that specifies the cell fate of immature T cell precursors towards the CD4 lineage. The researchers discovered that Th-POK is lineage restrictedly expressed in the luminal epithelial cells in mammary glands, in a manner similar to that in the T cell populations. Unlike that in the T cell development, Th-POK is dispensable for mammary epithelial cell lineage specification and mammary gland development. Rather, Th-POK plays pivotal roles in the secretory activation process to trigger proper onset of lactation and sufficient milk lipid production. Th-POK regulates the expression of insulin receptor sunstrate-1 and insulin-induced mTOR-SREBP pathway activation and lipid biosynthesis in the mammary alveolar cells at lactation. Thus, Th-POK functions as an important metabolic regulator in the lactating mammary glands. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner.

 

This work, entitled “Th-POK regulates mammary gland lactation through mTOR-SREBP pathway”, was published online in PLOS Genetics on Feb 8, 2018. It was supported by grants from the National Natural Science Foundation of China and the Strategic Priority Research Program of the Chinese Academy of Sciences. Dr. Yi Arial Zeng from SIBCB provided tremendous help in the study.

LINK：http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007211