2.CELL AND CELL DIFERRENTIATION class 2011.ppt

Notes

1. CELL AND CELL
DIFFERENTIATION
Dr. Alex Sanga MVM, MBA
SJUT
SOPH 2012, October

2. A Cell
Cell is a Latin word meaning small enclosures
may be defined as the smallest structural unit of a
living organism that can function independently if
placed in an appropriate environment.
Very few scientists on those early days who guessed the
significance of the cells,
Dutch biologist and microscopist Anton Van
Leeuwenhoekrevealed the mysteries and the
importance of the cell after the advancement of the
microscope.

3. A Cell…
It is the basic unit of all living organisms.
The human body has more than 300 trillion cells and it
is estimated that more than 10 million die and been
replaced in every second
Cell Theory-developed independently by both
Schleidenand Schwann in 1832. States that all living
organisms are constructed of small sub-units called
cells.

4. A Cell…
In 1665 English scientist Robert Hooke named the cells
when examined the cork slices.
In most of the organisms, the cell is the smallest
functional unit.
The cells form tissue which combine together to form
organ which in turn will form the system and the
systems will combine to form organism.

5. A Cell…
All precursor cells, also called stem cells , are alike and
omnipotent
They only differentiate into specialized cells as they
mature
Whether precursor or specialized, all body or somatic
cells have 46 chromosomes
Mature cells vary in size, shape, and function

6. A Cell…
Some common features of different
cells.
ability to exchange materials with their
immediately environment
obtaining energy from organic nutrients
synthesizing complex molecules
replicating themselves

7. A Cell…
An understanding of the cellular function is
important, because most disease processes are
initiated at the cellular level.
It must be noted that some diseases affect the cells of;
a single organ
others can affect the cells of a particular tissue type
and
others can affect the cells of entire organism

8. A Cell…
Consists of:
Cell membrane
Cytoplasm
Cytoplasmic organelles
Nucleus
Under EM

9. A Cell

10. A Cell

11. Introduction…
Depending on the types cells,
animals
can either be;
Eukaryotics or
Prokaryotics

12. Introduction….
eukaryotesare the cells of higher animals like wise
for the single-celled organisms fungi, protozoa
and most algae.
prokaryotesinclude cyanobacteria (blue-green
algae), bacteria and rickettsiae.
Prokaryotic and eukaryotic they differnot only in
their structure but also in chemical composition
and bio-chemical activity.

13. Introduction
prokaryotic cells
-carry genetic information in a single circular
chromosomes
-they lack proteins called histones.
-they lack true nucleus and nuclear membrane
-reproduce through simple fission
eukaryotic cells
-have several or many chromosomes.
-protein production or synthesis differs.
-different mechanism of transport across the
outer cellular membrane
-enzyme content is different.

14. Components of the cell
Under the light microscope, the cell has
nucleus
the cytoplasm and
cell membrane.
But in detailed analysis the cell comprises more than the
above

15. Components of the cell
Protoplasm has;
 the cytoplasm which lies outside the nucleus
and
 karyoplasmor nucleoplasmwhich lies inside
the nucleus

16. Components of the cell
Protoplasm
 Comprises of 70% to 85% as waterand 10% to 20%
of it bare the cell proteins.
 Lipidscomprise 2% to 3% of most cells.
 Carbohydratesare found in the cells but in small
amount for rapid source of energy.

17. Components of the cell
Protoplasm
Has electrolytes
Major intracellular electrolytes are; Potassium,
Magnesium, Phosphates, Sulphates and
Bicarbonates
Small intracellular electrolytes are;
Sodium, Chlorides and Calcium

18. The nucleus
large, spherical structure enclosed in a phospholipid
bilayer called nuclear envelope, situated near the center
of the cell
contains genetic material known as chromatin in the
nucleolus.
contains deoxyribonucleic acid (DNA) with genes as
genetic materials
layers are joined at openings; the nuclear pores
these pores are channels made up of more than 100
different proteins that allow movement in and out of
the nucleus

19. The nucleus
Control center of the cell
all eukaryotic cells have at least one nucleus but
some cells like osteoblasts contain 12 or more.
it has the site of ribonucleic acid (RNA) synthesis.
bound by phospholipid bilayer = nuclear membrane
it contains DNA
DNA replication = synthesis of DNA double strand
DNA transcription into mRNA m-RNA synthesis r-
RNA

20. RNA
There are three types of RNA in the
nucleus;
(mRNA) which copies and carries the DNA
instructions for protein synthesis to the cytoplasm
(rRNA) which moves to the cytoplasm, where it
becomes the site of protein synthesis
(tRNA) which moves into the cytoplasm to
transports amino acids

21. The cell membrane
outermost limit of the cell
separates the intracellular contents from the
extracellular environment.
it is a bimolecular layer that consists primarily of
phospholipids,with glycolipidsand cholesterol.
thin, flexible, elastic that maintains integrity of the
cell and controls entrance and exit of substances

22. The cell membrane
Is one of the most important parts of the cell.
it acts as semi permeable structure
it provides receptors
participates in the electrical events that occur in nerve
and muscle cells
it aids in the regulation of cell growth and proliferation
it has a role in the behaviour of cancer cells.
Selectively semi permeable receives and responds to
messages, signal transduction.

23. Cell Membrane Structure
It is a phospholipid bilayer.
It contains lipids, proteins, and glycolipids or glycoproteins
with some carbohydrates.
The surface of the membrane is formed by water-soluble
heads made up of phosphate groups ( hydrophilic or
polar )
The interior of the membrane is formed by water-
insoluble tails composed of fatty acids ( hydrophobic or
nonpolar )

24. Membrane Transport
Molecules that are soluble in lipids can easily pass
through the membrane.
Molecules that are water-soluble do not move through
the membrane.
Cholesterol molecules embedded inside of the lipid
bilayer make the cell membrane even more impermeable
and make it inflexible.

25. Movements Into and Out of
the Cell
The cell membrane controls the movement of
substances into and out of the cell.
Movements involve physical or passive processes such
as diffusion, facilitated diffusion, osmosis, and
filtration.
Movements can be physiological or active processes
such as active transport, endocytosis, and exocytosis.

26. Diffusion
Diffusion is the tendency of molecules, and ions in
solution to move from areas of higher concentration to
areas of lower concentration
The difference in concentration is the concentration
gradient .
Diffusion occurs because particles are in constant
motion attempting to equilibrate across a membrane
or inside an organelle.
Diffusion progresses until there is no net movement
any longer called diffusional equilibrium .

27. Diffusion in Living Systems
Diffusional equilibrium is more correctly referred to as
seeking of a physiological steady state .
Diffusion of substances occurs if the membrane is
permeable to that substance and if a concentration
gradient exists
E.g. oxygen, carbon dioxide, cholesterol

28. Facilitated Diffusion
Substances that are insoluble in lipids and too large to
move through pores move by facilitated diffusion.
Facilitated diffusion includes protein channels and
protein carriers.
Molecules fit into the carrier and are transported
across the membrane.
The number of carriers limits the rate of movement

29. Osmosis
Osmosis is the diffusion of water molecules from a region of
higher water concentration to a region of lower water
concentration across a selectively permeable membrane or
Osmosis is the diffusion of water molecules from a region of
low solute concentration to a region of high solute
concentration across a selectively permeable membrane.
Red Blood Cells (RBC) exhibit how osmosis works nicely:
when in isotonic or plasma solution, they appear donut shaped.
When they are placed into a hypotonic solution, they take up water and swell
and might even burst.
When they are placed into a hypertonic solution, they loose water and shrink in
size.

30. Filtration
Molecules can be filtered by force (such as pressure
differences) through membranes as is done in the
kidney nephrons.

31. Active Transport
It occurs when the net movement of particles passing
through membranes is in the opposite direction, from
a region of lower concentration to one of higher
concentration.
It utilizes protein carriers.
This process requires energy from cell metabolism.

32. Endocytosis and Exocytosis
Endocytosis moves particles too large to move by diffusion
or active transport.
Pinocytosis is the intake of liquid droplets.
Phagocytosis is the intake of solids, often with the fusion of
lysosomes which digest the material. Pinocytosis and phagocytosis
bring material indiscriminately into the cell.
Exocytosis often expels the residue after lysosomal enzymes
have digested solids brought in through phagocytosis.
Exocytosis allows cells to secrete material produced by the
cell e.g. neurotransmitters

33. Membrane Proteins
Fibrous proteins that span the membrane
function as receptors.
Globular,integralproteinsspanningthe
membraneallowpassageofcertainmoleculesor
ionssuchasthecysticfibrosistransporterprotein
(CFTR)thattransportschlorineacrossthecell
membrane.
Globular, peripheral proteins that do not span the
membrane function as enzymes or signal
transducers. These often aid in cell recognition
and cell binding of ‘growth factors’.

34. The cytoplasm and its
components
surrounds the nucleus
it is a colloidal solution that contains - -
water,
-electrolytes,
-suspended proteins
-neutral fats
-glycogen molecules
-sometimes pigments

35. Cytoplasm
The cytoplasm is a clear gel called cytosol
It contains a network of membranes around organelles that
are suspended in the cytosol.
Protein rods and microtubules form the cytoskeleton, a
supportive framework.
The many different organelles perform specific cellular
functions that aid in the growth of cells and the body.
Translation of m-RNA into protein using t-RNA

36. Organelles of the
cytoplasm
Endoplasmic reticulum (smooth and rough)
(RER) has ribosome attached to it for protein synthesis,
produces digestive enzymes and antibody proteins
(SER) contain enzymes that synthesize lipids and other
substances

37. Organelles of the
cytoplasm
The ribosomes
serve as sites of protein synthesis.
Golgi complex
these are sacs connected with the tubules of RER, where
large carbohydrates molecules are synthesized and
combined with the proteins
Membrane stacks looking like “Stack of Pancakes”;
cisternae post translational modification, transport and
packaging of proteins in vesicles

38. Organelles of the
cytoplasm
Lysosomes
membranous sac of digestive enzymes degradation of worn cell
parts (“autolysis) and foreign particles
digest materials that have been brought into the cell by
phagocytosis, contain powerful hydrolytic enzymes -acid
hydrolases, pH of approximately 5 in lysosomes
white blood cells contain lysosomes which aid in the digestion
of bacteria and degradation of bacterial components

39. Organelles of the
cytoplasm
Centrioles
they form mitotic spindle during cell division
Mitochondria
Fluid-filled sacs that contain their own DNA and can divide on
their own; their enzymes control reactions of energy release from
nutrients
are the “power plants” of the cell, by extracting energy from
organic compounds .
inner membrane is folded into “cristae”; cellular respiration ;
uses O 2 , releases CO 2 ,makes 38 ATP = energy

40. Organelles of the
cytoplasm
Peroxisomes
Membranous sacs filled with catalase enzymes (catalase) for
detoxification of harmful substances(i.e.ethanol,drugs) found
in all cells but abundant in liver and kidneys
contain several enzymes that either produce or use hydrogen
peroxide and are smaller than lysosomes
peroxidases, catalyze metabolic degradative reactions that
release hydrogen peroxide as a byproduct
Catalase decomposes hydrogen peroxide (H 2 O 2 )

41. Organelles of the
cytoplasm
Caveolae
can capture extracellular material and shuttle it inside
the cell or across the cell.
Proteasomes
is the place where the protein breakdown (proteolysis)
take place, recognize mis formed and mis folded
proteins

42. Organelles of the
cytoplasm
Vaults
arebarrel-shapedstructures,approximatelythreetimes
largerthanribosome
maybetheyareinvolvedinthetransportofmolecules
likemRNAbtnnucleusandcytoplasm
maybeinvolvedinthedevelopmentofresistanceto
cancerchemotherapy

43. The cytoskeleton
These are network of;
-microtubules,
-microfilaments,
-intermediate filamentsand
-thick filaments,
which support the structures, shapes and
movements such asphagocytosisof the
cell.

44. The cytoskeleton
Functions;
-mechanical support and structure,
-intracellular transport of material,
-suspension of organelles
-formation of adhesion with other cells

45. The cytoskeleton
Microtubules
are the largest cytoskeleton components
they contain globular protein called tubulin
involve in development and maintenance of cell form

46. The cytoskeleton
Microtubules
Microtubules are long, slender tubes composed of the
protein tubulin. They form the cytoskeleton and help
move organelles within the cells
participate in intracellular transport mechanisms
formation of the basic structure for several complex
cytoplasmic organelles including the centrioles, basal
bodies, cilia and flagella
essential for various stages of leukocytes migration

47. The cytoskeleton
Microfilaments
are tiny rods of the protein actin. They function
in cellular movements
Three classes of microfilaments exist
i.thin microfilaments
ii.thick myosin filaments
iii.intermediate filaments
intermediate filaments are important in supporting and
maintaining the asymmetric shape of cells.

48. Cell communication
There are three major ways of communication;
protein channels (gap junctions); desmosomes (macula
adherens), tight junctions(zonula occludens) and gap
junctions
receptors that affect the cell itself and other cells in
direct physical contact
they secrete chemical that signal to cells some distance away.
Secreted chemicals signals involve communication locally and at
a distance.
To coordinate their function and control their growth.

49. Cell communication

50. Primary modes of
chemical signaling
autocrine signaling
paracrine signaling
endocrine signaling
synaptic signaling
Alterations in cellular communication affect
disease onset and progression thereby
favouring cancerous tumour development.

51. Cell receptors
Can either be in the cell membrane (surface
receptors) or within the cells (intracellular
receptors).
they can recognize and bind with specific smaller
molecules called LIGANDSwhich must fit
together like pieces of jigsaw puzzle .
Receptors are activated by a variety of extracellular
signals or first messengers

52. Surface receptors
Three known classes of cell surface receptors proteins
exist;
-G-protein linked receptors
-Ion channel linked receptors
-Enzyme linked receptors

53. G-protein linked receptors
more than 1000 members and it is the largest group of cell
receptors
to be active or inactive they must be binded to guanine
nucleotides; guanine diphosphate (GDP) and guanine
triphosphate (GTP)
they mediate cellular responses for numerous types of first
messengers
Mediate the cellular response to an enormous diversity of
signaling molecules, including hormones, neurotransmitters,
odorants and photons
•Adrenaline activates 9 distinct G-protein-coupled receptors,
serotonin activates at least 15
•Half of all known drugs work through G-protein linked receptors

54. G-protein linked
receptors
They share a number of similar features;
all are found on the cytoplasmic side of the cell
membrane
all incorporate the GTPase cycle, which functions
as the on-off switch for response

55. Two major pathways by which G-protein
linked receptors signal.
Most G-protein-linked
receptors signal through
the second messengers
cyclic AMP or calcium.
In both cases, the activated
receptor binds to a
trimeric G-protein to
begin the signaling event.
Signaling
molecule
receptor
G-protein
enzyme
cAMP Ca
2+
Target
protein

56. Vibrio cholerae
causative agent of cholera
Spread via
-contaminated water
-raw or undercooked shellfish
problem in
-developing nations
-natural disasters
Symptoms
-abrupt, painless, watery diarrhea
-metabolic acidosis with potassium
depletion
-death

57. Effect of cholera
toxin
Persistent activation of adenylyl cyclase

58. G-protein linked
receptors
cholera toxin binds to a membrane ganglioside
(phospholipids with carbohydrate residues attached)
on the secretory cells in the small intestine
A -subunitof the toxin enters the cell and causes
activation of a G protein
this G protein activates adenylate cyclase

59. G-protein linked
receptors
adenylate cyclasecatalyzes the formation of cAMP
cAMPactivates protein kinases
protein kinasesenhance the secretion of chloride
ions
the flow of negatively charged chloride ionsout of
the cell causes positively charged sodium ionsto
follow them

60. G-protein linked
receptors
then water follows the elecrolytes into the lumen of
the small intestine by osmosis.
the presence of vibrio cholerae will cause production
of more toxins,which will in turn will cause
production of excess cAMPtherefore excess fluid and
electrolytes will be secreted into the lumen of small
intestine, resulting in severe diarrhea

61. The cell cycle
Is an ordered set of events, culminating in cell growth and division
into two daughter cells.
The series of changes that a cell undergoes from the time it forms
until it divides is called the cell cycle -is a life of the cell
It is usually divided into five phases or
gaps; G0, G1, S, G2 andM
•Interphase is the period of cell growth and function. Is
composed of G1, S Phase, and G2.

62. The cell cycle
The cell cycle has TWO
major stages;
Interphase (cell
growth and
development)and
cytokinesis (cell
division)

63. The cell cycle
G0is the stage during which the cell may leave the cell
cycle and either remain in a state of inactivity or
reenter the cell cycle at another time.
G1isthestagecellwhereisstartingtopreparefor
mitosisthroughDNAandproteinsynthesisandan
increaseinorganellesandcytoskeletonelements.Is
thefirstGaporGrowthphase.Duringthisperiod,cell
growthoccurs.

64. The cell cycle
Sis the synthesis phase, during which DNA replication
occurs and the centrioles are beginning to replicate.
G2is the pre-mitotic phase and it is similar to G1as for
RNA and protein synthesis. Is the second Gap or
Growth phase. During this period, the cell replicates
organelles in preparation for cell division
Mphase is the phase during which cell mitosis occurs.

65. Regulation of the cell cycle
Cell division is very complex.
where errors in regulation can lead to cancer. Cancer is a
disease where regulation of the cell cycle goes awry and
normal cell growth and behavior is lost.
Cdk(cyclin dependent kinase, adds phosphate to a protein), along with
cyclins, are major control switches for the cell cycle, causing the cell to move
from G1 to S or G2 to M.
MPF(Maturation Promoting Factor) includes the CdK and cyclins that triggers
progression through the cell cycle.
p53is a protein that functions to block the cell cycle if the DNA is damaged. If
the damage is severe this protein can cause apoptosis (cell death).
p27is a protein that binds to cyclin and cdk blocking entry into S phase. Recent
research suggests that breast cancer prognosis is determined by p27 levels.
Reduced levels of p27 predict a poor outcome for breast cancer patients.

66. p53
p53is a protein that functions to block the cell cycle if
the DNA is damaged. If the damage is severe this
protein can cause apoptosis (cell death).
p53 levels are increased in damaged cells. This allows time to
repair DNA by blocking the cell cycle.
A p53 mutation is the most frequent mutation leading to
cancer. An extreme case of this is Li Fraumeni syndrome, where
a genetic a defect in p53 leads to a high frequency of cancer in
affected individuals.

67. Cell divisions
Twowaysofcelldivision;mitosisandmeiosis
Mitosisisthecharacteristicofsomaticcells
Somematurecells,suchasskeletalandcardiacmuscles
cellsandnervecellsdonotdivide
Mitosisisdividedintofourstages;prophase,metaphase,
anaphaseandtelophase.

68. Mitosis
What is (and is not) mitosis?
Mitosis is nuclear division plus cytokinesis, and
produces two identical daughter cells during prophase,
prometaphase, metaphase, anaphase, and telophase.
Interphase is often included in discussions of mitosis,
but interphase is technically not part of mitosis, but
rather encompasses stages G1, S, and G2 of the cell
cycle.

69. Mitosis
In prophase
chromosome thickens and
shortens and become visible in
the light microscope
the centrioles migrate to
opposite poles of the cell and
form the mitotic spindle, which
consists of small fibers radiating
in all directions from the
centrioles
Some fibers cross the cell to
form the mitotic spindle.
the nuclear membrane breaks
down toward the end of
prophase

70. Mitosis
In metaphase
Spindle fibers align the
chromosomes along the middle
of the cell nucleus. This line is
referred to as the metaphase
plate. This organization helps to
ensure that in the next phase,
when the chromosomes are
separated, each new nucleus will
receive one copy of each
chromosome.
chromatids are partially
separated but still remain joined
at a constricted area called
centromereto which the spindle
fibers are attached.

71. Mitosis
In anaphase
chromosomes are pulled to
opposite poles of the cell by
spindle fibers
Thepairedchromosomes
separateatthekinetochores
andmovetooppositesidesof
thecell.Motionresultsfroma
combinationofkinetochore
movementalongthespindle
microtubulesandthrough
thephysicalinteractionof
polarmicrotubules.

72. Mitosis
In telophase
Chromatidsarriveatopposite
polesofcell,andnew
membranesformaroundthe
daughternuclei.
Thechromosomesdisperse
andarenolongervisible
underthelightmicroscope.
Thespindlefibersdisperse,
andcytokinesisorthe
partitioningofthecellmay
alsobeginduringthisstage.

73. Cytokinesis
Inanimalcells,cytokinesis
resultswhenafiberring
composedofaproteincalled
actinaroundthecenterofthe
cellcontractspinchingthecell
intotwodaughtercells,each
withonenucleus.
Inplantcells,therigidwall
requiresthatacellplatebe
synthesizedbetweenthetwo
daughtercells.

74. Meiosis
is a specialized type of cell division
it occurs in the process of gametogenesis.
it reduces the number of chromosomes by half
It entails two separate divisions called the first and the
second meiotic divisions.

75. Cell differentiation
Is the formation of different types of cells
in the human body there are approximately 200
different types of cells
the process is controlled by the cell memory
the process normally moves forward, producing
cells that are more specialized than their
predecessors
Many tissues contain a few stem cells that
apparently are only partially differentiated and
serve as a reserve source

76. cells can interact with each other and with their
environment
this interaction turns specific signaling paths ON or
OFF
these pathways become important for mediating
proliferation, differentiationand apoptosis
all three are crucial to development

77. Differentiation:
Stem cells
fertilization of the egg takes
place in the oviduct
the fertilized zygote travels to
the uterus for implantation
along the way –the zygote
begins to divide (mitosis)
2-cell, 4-cell, 8-cell embryonic
stages etc….
the embryo reaches a stage
called the morula= ball of
small cells (embryo has not
enlarged)
by the end of the first week
the second embryonic stage –
the blastocyst -forms

78. Stem Cells
•Stemcellsaremastercellswithtwoimportant
characteristics
–Unspecializedcellscapableoftheirownrenewal
–Abilitytodifferentiateintodifferentcelltypes
•Thestemcellsmayhavevariousdifferentiation
potentials
•Totipotent
•Pluripotent
•Multipotent
•Unipotent

79. Differentiation: Embryonic Stem cells
the ES cells are said to be totipotent –have the ability to specialize or differentiate into
ALLcells of the embryo
the blastocyst then begins a process of differentiation and these ES cells form populations
of stem cells with more restricted potentials
the ES cells first differentiate into two layers called the embryonic disc–divides the
blastocyst cavity into an amniotic cavityand a yolk sac(primitive hematopoietic organ)
these two layers then continue to differentiate into the three germ layersof the embyro
ectoderm, mesoderm and endoderm
the formation of these germ layers marks the gastrula embryonic stage
•the blastocyst is a hollow
ball of cells containing an
outer rings of progenitor
cells = trophoblast and an
inner mass of cells at one
end of the embryo = inner
cell mass
•it is these ICM cells that are
the source for the
derivation of embryonic
stem (ES) cells

80. Stem cells differentiation

81. The origin of different
tissues
Three layers of embryo; the outer -ectoderm, the middle
layer -the mesodermand the inner layer -the
endoderm
epitheliumhas its origin in all threeembryonic layers
connectivetissuedevelop from the mesoderm
muscletissuefrom the mesodermand ectoderm

82. Germ Layers
the ectoderm, mesoderm and endoderm are thought to be
made up of stem cells with a more restricted phenotype
when compared to ES cells BUT still capable of forming
multiple cell types within that lineage
e.g. pluripotent stem cells
interactions between signaling molecules produced by
these germ layers and with the developing ECM around
these tissues results in specific developmental events =
patterning
patterning requires the exposure of cells to a succession of
signals and subsequent activation of their associated
pathways

83. Cellular interactions in development:
Induction
interactions between the cells of the germ
layers influence the fate of the stem cells
within these layers
can affect their differentiation paths
induction= mechanism where one cell
population influences the development of
neighbouring cells
e.g. mesoderm induces the overlying
ectoderm to form neural tissue
embryonic development is a series of
inductive events
binary–have a choice between one fate or
another (presence of one signal –
development down one path, absence of
signal –development down another path
gradient –multiple fates may result –
dependent upon the level or threshold of the
signaling molecule (these signaling molecules
are called morphogens)
relay –a signal induces a cascade which
determines the fate of cells in proximity –
these cells than produce additional signals
which affect the fate of their neighbours

84. Assignment
Write on the Bordetella pertussis
What is it?
The disease it causes
Pathogenesis of the disease
The difference in pathogenesis with cholera
Treatment of the disease
New roman 12 font, three pages, 1.5 spacing to be
submitted in our next class.

85. As I grow older, I pay
less attention to what
men say, I rather watch
what they do.
Changes can be delayed
but it is a MUST
29
th
10 2012