This document discusses pluripotency and self-renewal in stem cells. It explains that pluripotency allows a cell to differentiate into any of the three germ layers, and is a property of cells in the embryo. Self-renewal allows stem cells to divide and maintain the stem cell pool. Key transcription factors like Oct4, Nanog, and Sox2 regulate pluripotency and self-renewal by cooperating with each other. Knocking down Oct4 and Nanog can lead to differentiation, while maintaining their optimal expression levels inhibits differentiation and promotes self-renewal. Oct4 and Nanog also regulate genes involved in proliferation and differentiation. Telomerase helps stem cells maintain telomere length

1. REGULATION OF
PLURIPOTENCY AND
SELF-RENEWAL
STEM CELL
LUCKY MOYENGWE
”It isa humanbeingbiologically...there issomething
special aboutthe embryoandmostpeople tie that
specialnesstothe potentialityof itbecominga
person,because it alreadyisahuman being.Andthat
inrecognitionof that,we are goingto holdourselves
accountable intermsof how we interactwith,engage
or destroythe embryo.”-Francoise Baylis,ethicist,
Dalhousie University
16000314

2. Pluripotency, the ability of a cell to give rise to differentiated derivatives that represent each of the
three primary germ layers, and it is a property found on the cells located within the inner cell mass
of the developing blastocyst. Self-renewal can be defined as cells division to make more stem cells,
perpetuating the stem cell pool or maintenance of the undifferentiated state after cell division.
There are a group of transcription factors, the pluripotency transcription factors that affect the
pluripotent capacity and self-renewal which are Oct4, Nanog and Sox2. These transcription factors
are crucial for the efficient maintenance of pluripotent cell identity and self-renewal.1 During
embryo development, the specification of pluripotent cell identity requires the embryonic genome
to express Oct4 and Nanog and Sox2. perhaps owing to the presence of long-lived maternal Sox2
protein. Pluripotency transcription factors regulate stem cell pluripotency and aelf renewal via
cooperation with each other.
Differentiation potential and expression of developmental markers and tissue-specific genes are
decreased in the expression of Oct4 and Nanog. Expression of Oct4 and Nanog knocks down the
p21 pathway which is a potent cyclin-dependent kinase inhibitor and can lead to cell cycle arrest
and inhibit cell division. The expression of Oct4 and Nanog was not only localized in the nucleus
but associated with a less methylated pattern in the CpG regions of their promoters. Knockdown
of Oct4 and Nanog induced the expression of developmental markers and tissue-specific genes,
while overexpression of Oct4 and Nanog induces differentiation potential. This suggest that to
maintain pluripotency and self-renewal an optimum amount of oct4 is needed by the cell to inhibit
spontaneous differentiation.
Oct4 and Nanog directly bind to the promoter of Dnmt1 and enhance Dnmt1 expression, and this
binding lead to downregulation of the expression of cell cycle regulators including p21, p16 and
development and lineage genes. Oct4 and Nanog work together to regulate downstream genes.
Oct4 and Nanog cooperatively induce Dnmt1 expression to regulate the proliferative and
undifferentiated states of stem cells. Nanog control their downstream genes through indirectly
controlling their expression by binding to the Dnmt1 promoter. They identified that high levels of
Oct4 and Nanog, rather than Sox2, are indispensable for maintaining self-renewal in stem cells.
Oct4 directly inhibits the BMP4 signaling pathway, which activates mesoderm and
extraembryonic ectoderm or endoderm differentiation, while Nanog acts as a repressor of neural
crest and neuroectoderm lineage
Telomeres are nucleoprotein complexes located at the ends of chromosomes that prevent against
chromosomal instability and degradation during cell division. The DNA component of telomeres
is composed of tandem repeats with a 3' single-stranded overhang that invades telomeric duplex
DNA to form a protective loop. In somatic cells, telomeres shorten during repeated number of cell
division. To combat this process stem cells, maintain their telomeres using one of the enzyme
telomerase which is always highly activated or expressed during embryonic development of stem
cell. Telomerase is a reverse transcriptase enzyme made up of an RNA moiety that provides a
template for telomeric DNA synthesis and protein moiety that facilitates telomerase recruitment
and carries out its polymerase activity.