Open AccessRegulation and Expression of the ATP‐Binding Cassette Transporter ABCG2 in Human Embryonic Stem Cells
Author(s) -
Padmanabhan Raji,
Chen Kevin G.,
Gillet JeanPierre,
Handley Misty,
Mallon Barbara S.,
Hamilton Rebecca S.,
Park Kyeyoon,
Varma Sudhir,
Mehaffey Michele G.,
Robey Pamela G.,
McKay Ronald D. G.,
Gottesman Michael M.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1195
Subject(s) - biology , abcg2 , embryonic stem cell , embryoid body , microrna , microbiology and biotechnology , stem cell , atp binding cassette transporter , transporter , gene , adult stem cell , genetics
The expression and function of several multidrug transporters (including ABCB1 and ABCG2) have been studied in human cancer cells and in mouse and human adult stem cells. However, the expression of ABCG2 in human embryonic stem cells (hESCs) remains unclear. Limited and contradictory results in the literature from two research groups have raised questions regarding its expression and function. In this study, we used quantitative real‐time PCR, Northern blots, whole genome RNA sequencing, Western blots, and immunofluorescence microscopy to study ABCG2 expression in hESCs. We found that full‐length ABCG2 mRNA transcripts are expressed in undifferentiated hESC lines. However, ABCG2 protein was undetectable even under embryoid body differentiation or cytotoxic drug induction. Moreover, surface ABCG2 protein was coexpressed with the differentiation marker stage‐specific embryonic antigen‐1 of hESCs, following constant BMP‐4 signaling at days 4 and 6. This expression was tightly correlated with the downregulation of two microRNAs (miRNAs) (i.e., hsa‐miR‐519c and hsa‐miR‐520h). Transfection of miRNA mimics and inhibitors of these two miRNAs confirmed their direct involvement in the regulation ABCG2 translation. Our findings clarify the controversy regarding the expression of the ABCG2 gene and also provide new insights into translational control of the expression of membrane transporter mRNAs by miRNAs in hESCs. S TEM C ells 2012;30:2175–2187