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HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos,
primordial germ cells and stable cell lines
#MMPMID27605307
Yunusov D
; Anderson L
; DaSilva LF
; Wysocka J
; Ezashi T
; Roberts RM
; Verjovski-Almeida S
Sci Rep
2016[Sep]; 6
(?): 32753
PMID27605307
show ga
Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs
(lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-,
tissue-, and cell-subtype-specificity of expression, and are generally less
abundant in a population of cells. Despite the progress in single-cell-focused
research, the origins of low population-level expression of lncRNAs in
homogeneous populations of cells are poorly understood. Here, we identify HIPSTR
(Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus
RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR
has evolutionarily conserved expression patterns, its promoter is most active in
undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP
cells predominantly affects the genes involved in early organismal development
and cell differentiation. Most importantly, we find that HIPSTR is specifically
induced and heterogeneously expressed in the 8-cell-stage human embryos during
the major wave of embryonic genome activation. We systematically explore the
phenomenon of cell-to-cell variation of gene expression and link it to low
population-level expression of lncRNAs, showing that, similar to HIPSTR, the
expression of thousands of lncRNAs is more highly heterogeneous than the
expression of mRNAs in the individual, otherwise indistinguishable cells of
totipotent human embryos, primordial germ cells, and stable cell lines.
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