Human embryonic stem cells express a unique set of microRNAs.
Human embryonic stem (hES) cells are pluripotent cell lines established from the explanted inner cell mass of human blastocysts. Despite their importance for human embryology and regenerative medicine, studies on hES cells, unlike those on mouse ES (mES) cells, have been hampered by difficulties in culture and by scant knowledge concerning the regulatory mechanism. Recent evidence from plants and animals indicates small RNAs of approximately 22 nucleotides (nt), collectively named microRNAs, play important roles in developmental regulation. Here we describe 36 miRNAs (from 32 stem-loops) identified by cDNA cloning in hES cells. Importantly, most of the newly cloned miRNAs are specifically expressed in hES cells and downregulated during development into embryoid bodies (EBs), while miRNAs previously reported from other human cell types are poorly expressed in hES cells. We further show that some of the ES-specific miRNA genes are highly related to each other, organized as clusters, and transcribed as polycistronic primary transcripts. These miRNA gene families have murine homologues that have similar genomic organizations and expression patterns, suggesting that they may operate key regulatory networks conserved in mammalian pluripotent stem cells. The newly identified hES-specific miRNAs may also serve as molecular markers for the early embryonic stage and for undifferentiated hES cells.
Suh
Mi-Ra
MR
Cell and Gene Therapy Research Institute, Pochon CHA University College of Medicine, Seoul 135-081, South Korea.
Lee
Yoontae
Y
Kim
Jung Yeon
JY
Kim
Soo-Kyoung
SK
Moon
Sung-Hwan
SH
Lee
Ji Yeon
JY
Cha
Kwang-Yul
KY
Chung
Hyung Min
HM
Yoon
Hyun Soo
HS
Moon
Shin Yong
SY
Kim
V Narry
VN
Kim
Kye-Seong
KS
D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology*; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000235:genetics; D019295:Computational Biology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D035683:MicroRNAs