Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis.
During the transition from the inner cell mass (ICM) cells of blastocysts to pluripotent embryonic stem cells (ESCs) in vitro, a normal developmental program is replaced in cells that acquire a capacity for infinite self-renewal and pluripotency. We explored the underlying mechanism of this switch by using RNA-Seq transcriptome analysis at the resolution of single cells. We detected significant molecular transitions and major changes in transcript variants, which include genes for general metabolism. Furthermore, the expression of repressive epigenetic regulators increased with a concomitant decrease in gene activators that might be necessary to sustain the inherent plasticity of ESCs. Furthermore, we detected changes in microRNAs (miRNAs), with one set that targets early differentiation genes while another set targets pluripotency genes to maintain the unique ESC epigenotype. Such genetic and epigenetic events may contribute to a switch from a normal developmental program in adult cells during the formation of diseased tissues, including cancers.
Tang
Fuchou
F
Wellcome Trust/Cancer Research, UK.
Barbacioru
Catalin
C
Bao
Siqin
S
Lee
Caroline
C
Nordman
Ellen
E
Wang
Xiaohui
X
Lao
Kaiqin
K
Surani
M Azim
MA
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods*
D035683:MicroRNAs
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