San Diego
Regenerative Medicine Institute and Xcelthera
announce the publication of Dr. Parsons’ original research article supported by
the National Institutes of Health, titled “Genome-Scale Mapping
of
MicroRNA Signatures in Human Embryonic Stem Cell Neurogenesis”, in Molecular
Medicine & Therapeutics at http://dx.doi.org/10.4172/2324-8769.100010
& http://www.scitechnol.com/2324-8769/2324-8769-1-105.php
.
Understanding
the much more complex human embryonic development has been hindered by the
restriction on human embryonic and fetal materials as well as the limited
availability of human cell types and tissues for study. In particular, there is
a fundamental gap in our knowledge regarding the molecular networks and
pathways underlying the CNS and heart formation in human embryonic development.
The enormous diversity of human somatic cell types and the highest order of complexity of human genomes,
cells, tissues, and organs among all the eukaryotes pose a big challenge for characterizing, identifying, and
validating functional elements in human embryonic development in a
comprehensive manner. Derivation of human embryonic stem cells (hESCs)
provides a powerful in vitro model
system to investigate the molecular controls in human embryonic development as
well as an unlimited source to generate the diversity
of human cell types and subtypes across the spectrum of development
stages for repair. Development and utilization of hESC models of human
embryonic development will facilitate rapid progress in identification of molecular and genetic therapeutic
targets for the prevention and treatment of human diseases. To
tackle the shortcomings in conventional approaches, previously, we found
that pluripotent hESCs maintained under the
defined culture conditions can be uniformly converted
into a specific lineage by small molecule
induction. Our innovative small
molecule direct induction approach renders a cascade of neuronal or cardiac
lineage-specific progression directly from the pluripotent state of hESCs,
providing much-needed in vitro model systems for investigating
the human CNS development and heart formation in embryogenesis. This technology breakthrough not only opens the door
for further identification of the developmental networks in human embryonic
neurogenesis and cardiogenesis
in a comprehensive manner, but also offers means for small-molecule-mediated
direct control and modulation of the pluripotent fate of hESCs when deriving an
unlimited supply of clinically-relevant lineages for regenerative medicine.
Recent advances in large-scale profiling of
developmental regulators in high-resolution provide powerful genome-wide
high-throughput approaches that will lead to great advances in our
understanding of the global phenomena of human embryogenesis. Profiling novel
hESC models of human embryonic neurogenesis and cardiogenesis using genome-wide
approaches, including employing ChIP-on-chip and microRNA mapping, will reveal
molecular controls and the underlying mechanisms in hESC neuronal and
cardiomyocyte fate decisions. Unveiling developmental networks during human
embryonic neurogenesis and cardiogenesis using novel hESC models will
contribute tremendously to our knowledge regarding molecular embryogenesis in
human development, thereby, reveal potential therapeutic targets and aid the
development of more optimal stem-cell-mediated therapeutic strategies for the
prevention and treatment of CNS and heart diseases. The outcome
of such research will potentially shift current research to create new
scientific paradigms for developmental biology and stem cell research.
MicroRNAs
are small, evolutionarily conserved non-coding RNAs that modulate
gene expression by inhibiting mRNA translation and promoting mRNA degradation. MicroRNAs act as the governors of gene expression
networks, thereby modify complex cellular phenotypes in development or disorders.
MicroRNA expression profiling using microarrays is a powerful high-throughput
tool capable of monitoring the regulatory networks of the entire genome and
identifying functional elements in development in high resolution. To uncover key regulators in human CNS development during
embryogenesis, in this Dr. Parsons’ research
article, genome-scale profiling of microRNA differential expression
patterns during hESC neuronal lineage-specific
progression was used to identify novel sets of stage-specific human embryonic
neurogenic microRNAs. We found that the prominent pluripotence-associated
microRNAs were silenced and microRNAs involved in developmental networks were
drastically up-regulated. Our findings suggest that these hESC neuronal
derivatives have acquired a neuronal lineage-specific identity by silencing
pluripotence-associated miRNAs and inducing the expression of miRNAs linked to
regulating human CNS development to high levels, therefore, highly neurogenic in vitro and in vivo. Our study provides
critical insight into molecular neurogenesis in human embryonic development as
well as offers an adequate human neurogenic cell source in high
purity and large quantity for CNS
tissue engineering and developing safe and effective stem cell therapy
to restore the lost nerve tissue and function.
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