Biology Reference
In-Depth Information
3.3.1
The Role of MicroRNAs in Tissue Development
It is now emerging that miRNAs function in essentially all stages of tissue development.
MicroRNAs play key roles from the very onset of human development, the growth of
undifferentiated embryonic stem cells into a foetus with differentiated germ layers as
well as in adult tissue repair such as those found after a bone fracture.
3.3.1.1
MicroRNAs and Embryonic Development
The involvement of miRNAs in embryonic development is interesting as it illus-
trates their immense capacity for controlling the progression of cell differentiation;
furthermore, the therapeutic use of embryonic stem cells in clinical trials has started
[
26
]. At the earliest stages of life, the embryonic stem cells are kept undifferentiated
and pluripotent by a self-regulating circuitry of key proteins including OCT4, SOX2
and KLF4 which are silenced by miR-145 upon differentiation [
27
] . When cells
begin to differentiate into the earliest progenitor cells specific to the three germ lay-
ers, the endo-, meso- and ectoderm lineages, the cell identity is controlled, in part,
by microRNAs. In mice, for example, mesodermal specialisation is blocked by
microRNA members of the miR-290 cluster [
28
]. These miRNAs repress the expres-
sion of DKK1, an inhibitor of the WNT pathway, which plays a complex role in
embryonic cell specialisation. During increased specialisation, waves of successive
miRNAs are expressed. A study detailing miRNA expression at various develop-
mental stages during embryonic stem cell to adipocyte differentiation found that the
expression level of 129 individual miRNAs changed twofold or greater during dif-
ferentiation [
29
]. At the mesodermal progenitor stage after just 5 days, the expres-
sion levels of 104 miRNAs differed from the outset. Cell specialisation continues
throughout development and is activated in many tissues in the adult body when cell
populations need replenishing. We shall now explore this further.
3.3.1.2
MicroRNAs and Adult Tissue Development
In the adult, stem cells are located in specialised niches in most organs. An example
of adult stem cells is the neural stem cells that reside in the subventricular zone in
the brain and which are capable of generating new neurons, glia and astrocytes [
30
] .
Another example is the mesenchymal stem cells (MSCs) which are found in the
stromal compartment of many tissues such as bone marrow (BMSCs) and adipose
tissue (ADSCs). MSCs are, at least, capable of generating bone cells (osteoblasts),
cartilage cells (chondrocytes), fat cells (adipocytes) and muscle cells (myoblasts)
[
31
]. Adult stem cells are either activated upon tissue damage or are continually
active if replacing constantly removed cells, such as in the case of hematopoietic
stem cells. Activation leads to proliferation and differentiation of a subpopulation of
the stem cells into new specialised cells that replace or replenish the needed cells.
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