STEM CELLS

➢ Are defined by their capabilities to SELF-RENEW and give rise to various types of
differentiated cells depending on their POTENCY.

➢ They are classified as PLURIPOTENT, MULTIPOTENT, AND UNIPOTENT as demonstrated

through their potential to generate the variety of cell lineages.

➢ PLURIPOTENT STEM CELLS may give rise to all types of cells in an organism.

➢ MULTIPOTENT AND UNIPOTENT STEM CELLS remain restricted to the particular tissue
or lineages.

➢ CELL LINEAGE – traces the birth order of cells progressively becoming more restricted
in developmental potential and differentiating into specialized cell types.
link
CELL POTENCY refers to the varying ability of stem cells
to differentiate into specialized cell types. Cells with the
greatest potency can generate more cells types than
those with lower potency.

• Totipotent stem cells can give rise to any of the cell

types found in an embryo as well as extra-embryonic
cells (placenta): inner cells

• Pluripotent stem cells can give rise to all cell types of

the body (but not the placenta).

Embryonic stem (ES) cells: pluripotent

• Multipotent stem cells can develop into a limited

number of cell types in a particular lineage.

• Unipotent cells
• Differentiated cells: mature cell state

Cell Potency link

https://stemcells.nih.gov/info/basics
https://www.nature.com/subjects/stem-cell-therapies
 Early Mammalian development and embryonic stem cells

Blastocoel cavity

PLURIPOTENT CELLS

During embryogenesis, the zygote undergoes

numerous cell divisions, both symmetric and
OOCYTE, carrying a set of asymmetric, ultimately giving rise to an entire
chromosomes from the organism.
mother, and the sperm, Eight-cell stage embryo: Each cell is TOTIPOTENT to
carrying a set of give rise to a complete animal and divides to form
chromosomes from the the 16-cell morula; Blastocyst (64 cells) formation:
father. fluid inflow fills an internal blastocoel cavity.
 PLURIPOTENT CELLS

➢ Cells of the inner cell mass can be cultured in defined

media, forming EMBRYONIC STEM (ES) CELLS.

Blastocyst is formed
early in 5 days after
fertilisation.
ES cells can be maintained in culture and can form differentiated cell types

Human blastocysts – grown from

cleavage-stage embryos produced by in
vitro fertilization

INNER CELL MASS: Separated from

surrounding extraembryonic tissues;
plated onto a layer of fibroblast cells –
provide specific protein
hormones/growth factors-to
EMBRYONIC STEM CELLS (ES CELLS).
These cells can also be maintained in
vitro by the addition of specific growth
factors and cytokines.

Individual cells – form ES cell colonies –

can be maintained for many
generations/stored frozen
 Basic transcriptional network regulating pluripotency of ES cells
Three master transcription factors – Oct4, Sox2, and Nanog

ES CELLS PLURIPOTENCY IS CONTROLLED BY MULTIPLE FACTORS, INCLUDING THE STATE OF DNA METHYLATION,
CHROMATIN REGULATORS, CERTAIN MICRO-RNAS, AND TRANSCRIPTION FACTORS.
➢ Unlike ES cells, the STEM CELLS IN ADULTS ARE MULTIPOTENT: they can give rise
to some of the types of differentiated cells found in the organism, but not all of
them.

➢ Human derived Embryonic Stem Cells (ESCs)-PLURIPOTENT are demonstrated to

generate all types of cells but lack potential to contribute to the extra-embryonic
cells such as placenta. These cells various functional properties depending on
their culture conditions.

➢ Another important class of stem cells is LINEAGE SPECIFIC MULTIPOTENT STEM

CELLS [e.g., HEMATOPOIETIC STEM CELLS (HSCS)
Overview of the birth, lineage, and death of cells

Cell lineage with a series of symmetric and asymmetric cell divisions .

 Stem Cells and cell asymmetry

• SYMMETRIC CELL DIVISION yields identical daughter cells that may have different
fates if exposed to different external signals.

• ASYMMETRIC CELL DIVISION yields two different types of daughter cells with
different fates.

• Embryonic blastocyst inner mass cells are pluripotent and give rise to all
differentiated cell types of the organism.
 Stem Cells and Niches in Multicellular Organisms

• Most animal stem cells are multipotent and can undergo symmetric or asymmetric self-
renewal divisions.

• MULTIPOTENT SOMATIC STEM CELLS constitutes the most common type of stem cells,
giving rise to both stem cells and specialized cells composing the body tissues. They can
reproduce themselves during many cell divisions (self-renewal) and the ability to generate
progeny of more restricted potential.

• Stem cells are formed in niches that provide signals to maintain a population of
undifferentiated stem cells but prevent excess proliferation.

• Stem cells regenerate differentiated tissue cells that are damaged, sloughed, or aged.
 The pathway from stem cells to lineage-restricted progenitors
to differentiated cells

Multipotent somatic
stem cells

Divide rapidly and undergo limited self-

renewal divisions. Produce lineage-
restricted progenitor cells. Divide and Cannot undergo self-renewal divisions
produce specific differentiated cells.
 Patterns of stem-cell differentiation

Asymmetric divisions

Symmetric and asymmetric divisions may occur simultaneously

DURING NORMAL DEVELOPMENT HORMONES SECRETED BY OR ON THE SURFACE

OR INJURY RECOVERY OF ADJACENT CELLS REGULATE THESE PATTERNS
OF STEM CELL DIVISION.
 Stem cells for diferent tissues occupy sustaining niches

➢ Hundreds of EXTRACELULAR SIGNALLING MOLECULES regulate the growth and fate of the cells.

➢ These signalling molecules can have both short- and long-term effects on cells.

➢ SHORT-TERM EFFECTS: MODIFICATION OF EXISTING ENZYMES OR OTHER PROTEINS

➢ LONG-TERM EFFECTS: REQUIRE CHANGES IN GENE EXPRESSION-ALTER CELL DIVISION AND CELL
DIFFERENTIATION
➢ CYTOKINES- SIGNALLING MOLECULES induce the production of different cells, like red blood cells,
leukocytes and platelets. Once differentiated, cells respond to the environment by changing their shape,
metabolism, or movement by changes in gene expression.
Examples: Hormones
 Several common types of cell-surface receptors and signal transduction
pathways
Many receptor cytosolic domains are protein kinases or tightly
Receptor-associated kinases: activated by protein growth factors associate with a cytosolic kinase.

Ligand binding causes

receptor dimerization
which activates kinase
activity: directly
phosphorylate and activate
transcription factors or
other signaling proteins

Signalling
molecules
G protein coupled receptors (GPCR)
Induction of a particular gene by a transcription factor depends not only on binding
sites for the factor, but also on the gene’s epigenetic state and on the presence of
master transcription factors and other nuclear proteins.

An activated transcription factor (Tf)

can bind to multiple chromosomal
DNA sites such as gene enhancers in
an “open chromatin” conformation
that has cell-specific master
transcription factors or other
proteins bound to adjacent sites.

Many genes are regulated by

multiple transcription factors
activated or repressed by different
intracellular signaling pathways that
are activated by different
extracellular signals.