Jeanne A Pawitan

Cell and genetics –histology 2007

• Cells ° Stem cells° Cells of the 4 basic tissues° Other specialized cells

• Jeanne Adiwinata Pawitan

Dept. of Histology FMUI

Jeanne A Pawitan

Stem cells

Jeanne A Pawitan

Stem cells – ability to differentiate

Totipotent = all +

placenta

Pluripotent = all

Multipotent = several

Unipotent = 1 type -

><mature: self renewal

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Stem cells - source

• Embryonic stem cells (inner cell mass)

• Adult stem cells: bone marrow, umbilical cord blood, Wharton jelly, adipose tissue, etc. ° Multipotential - > determined – adult stem cells

in 1 lineage: connective tissue, blood, etc° Unipotential – progenitors (commited) 1 cell line

→ differentiation → precursor → mature fully differentiated cells

Jeanne A Pawitan

Cells of the 4 basic tissues

• Epithelium: cells, intercellular substance/extracellular

matrix – basement membrane

• *Connective tissue: intercellular substance↑

• Muscle: muscle cells* = muscle fibers

• Nerve*: ° Neurons ° Neuroglial cells (support, protect neurons)

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Epithelium

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Epithelium (and glands)

• Layers ° Single

• Simple• (Pseudostratified)

° Multiple • Stratified • (Transitional)

• Shape ° Squamous

° Cuboidal

° Columnar (torax)

• Location

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Jeanne A Pawitan

Polarity and cell surface specializations

• Morphological domain

• Biochemical domain Polarity

• Functional domainApical domain – free surface – lumenBasolateral domain

Basal - basal laminaLateral – other cells

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Apical domain - lumen

• Microvilli • Cilia

° Kinocilia° Stereocilia

• Ion channels• Aquaporins• Carrier proteins• H+- ATPase• Glycoproteins• Hydrolytic enzymes

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Basolateral domain

• Intercellular interdigitation, basal enfoldings

• Junctional specialization

• Receptors ° Hormones° Neurotransmitters

• Na+-K+ ATPase

• Ion channels

• Sites for constitutive secretions

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Junctional specialization

• Lateral membrane specialization – terminal bars (LM) – junctional complexes (EM)° Occluding junction, tight

junction, zonula occludens

° Adhering junction• Zonula adherens -zonulae

adherentes

• Fascia adherens

• Macula adherens (desmosome) - hemidesmosome

° Gap junction

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Epithelial cellsSimple squamous Endothelium,

mesothelium

Simple cuboidal, columnar

Stratified cuboidal, columnar

Glands

Pseudostratified Respiratory S.

Transitional Urinary S.

Stratified squamous – keratin + Epidermis-skin

Stratified squamous – keratin - Mucous membrane: oral, esophagus, vagina

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Connective tissue

Jeanne A Pawitan

Connective tissues• Mesenchyme (embryo) – mucosa /gelatinosa • Connective tissue proper

° Loose (areolar) connective tissue areolar CT° Reticular connective tissue° Adipose tissue° Dense connective tissue

• Dense regular connective tissue Dense regular collagenous connective tissue Dense regular elastic connective tissue

• Dense irregular connective tissue

• Specialized connective tissue (cartilage, bone, blood)

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Intercellular substance/ extracellular matrix

• Ground/amorphous substance (gel like)– tissue fluid° Glycosaminoglycans (GAG) (hyaluronic acid, heparin,

sulfated GAG)° Proteoglycans ( certain GAG – Protein)° Adhesive glycoproteins (fibronectin, laminin, entactin,

tenascin, chondronectin, osteonectin)• Fibers

° Collagen type I – VII• Reticular (type III collagen)

° Elastic fibers

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Cells of connective tissue

• Cells of mesenchyme ° Mesenchymal cells

• Cells of loose connective tissue

• Cells of reticular CT ° Reticular cells

° Lymphocytes

° Plasma cells

• Cells of cartilage

• Cells of bone• Cells of blood

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Loose connectine tissue

• Fixed cells ° Fibroblasts/fibrocytes° Histiocytes/macrophages° Mast cells° Pericytes° Adipose cells

• Transient cells: ° plasma cells° leucocytes ° macrophages

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Cells of cartilage

Chondrogenic cellsChondroblast

ChondrocyteShrunkenlacuna

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Cells of boneOsteogenic cellsOsteoblastOsteocyteOsteoclast

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Cells of blood

ErythrocyteLeucocyte

NeutrophilEosinophilBasophilMonocytelymphocyte

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Basement membrane

• Basal lamina° Lamina lucida

° Lamina densa

• Lamina reticularis: type I, III collagen

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Muscles

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Muscles• Striated muscle – characteristic striation –

specific arrangement of myofilament (contractile protein in a myofibril: myosin, actin) parallel arrays regularly repeated arrangement interdigitating in myofibril° skeletal muscle° cardiac muscle

• Smooth muscleMyoepithelial cells –glandular unit in glandsMyofibroblast – wound contraction, tooth

eruption

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Unique terms in muscle

• Sarcolemma = cell membrane

• Sarcoplasm = cytoplasm

• Sarcoplasmic reticulum = smooth surfaced endoplasmic reticulum (SER)

• Sarcosome = mitochondria

• muscle fiber = muscle cell

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Smooth muscle• Location: wall of hollow organ - lumen

° Digestive system

° Reproductive system

° Urinary system

° Respiratory system

° Ducts - large (glands)

° Dermis (skin)

• Function:° contraction

° Protein synthesis extra cell: collagen, elastin, glycosaminoglycans, proteoglycans, growth factors

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Smooth muscle

• contraction - involuntary – controlled by° Autonomic nervous system (sympathetics,

parasympathetics)

° Hormone: bradykinin

° Local physiological condition

• Every fiber – lined by external lamina (outside sarcolemma)° reticular fiber - embedded in external lamina –

surrounding each muscle cell – function: control and unify the strength of muscle fiber contraction

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Smooth muscle

fiber

• Shape : fusiform, elongated –Ø 5-6 μm, length -0.2 mm

• Surrounded by sarcolemma (cell membrane)

• Nucleus - center – oval – 1-2 nucleolei – at contraction nucleus bottle opener

• HE: cytoplasm – homogenous – acidophilic

• Iron hematoxylin – in sarcoplasm: ° Dense body – attached at the

inside of cell membrane

° Longitudinal lines groups of myofilaments

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Smooth muscle fiber

• Form sheets/layers – usually 2 layers – perpendicular

• fibers –closely packed – thin part >< thick part° Cross section – fiber diameter ≠ – section -

nucleus (+)/(-)

• Individual cell

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Innervation – smooth muscle fiber• Neuromuscular junction usually en passant type

° Bulging of axon° Containing synaptic vesicles

• Nor epinephrine – sympathetic• Acetylcholine – parasympathetic

• Type ° multi unit –individual innervation (iris, vas deferens° Intermediate (mixed 30-60% - individual)° Visceral – some fibers – 1 neuromuscular junction – gap

junction/nexus (uterus, GI tract) – other influencing factor

• Humoral factor : oxytocin• Micro environmental factor : stretching (intestines)

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Cardiac muscle• Development: Myoepicardial mantle in

splanchnic mesenchyme epicardium + myocardium

• Cardiac muscle ° Cardiac muscle fiber–branching-anastomosing

network – arranged in layers (laminae) ° Between fibers – connective tissue° Connective tissue between laminae – contains:

• Blood vessels capillaries network –in connective tissue between each fiber

• Nerves • conducting system – in heart

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Cardiac muscle fiber

• Striated, branching

• Length 15-80 μm

• Nucleus 1 (occasionally 2) – center – big –oval

• Perinuclear space

• Between cells (at the end) - intercalated disk -consist of:

° Transverse portion: facia adherens ( Z disk), desmosome

° Lateral portion: gap junction (also found in regions - side by side contact – long.)

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Sarcoplasm contains• Myofibrils Ø-1-2 μm –longitudinal –regularly

arranged striated (longitudinal section): ° A band – (anisotropic on polarized light dark) ° I band– (isotropic on polarized light)

• EM: Sarcoplasmic reticulum = SER ° Network around myofibril° Function: intracellular Ca storage (< skeletal muscle)° Small terminals (terminal cisternae -) ° The rest = longitudinal sarcotubule + branches ° Contraction needs active transport of Ca from extra cell

• membrane contains junctional feet (= voltage gated Ca release channels)

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Sarcoplasm contains

• Organels° Mitochondria >>> - ½ volume – cardiac

muscle° Myoglobin O2 transport° Glycogen particle energy source for

contraction ( with lipid)

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Cardiac muscle fiber – T tubule

• EM: Sarcolemma – tubular invagination – transverse – branching - anastomosing T tubule (transverse tubule)

• Intertwine among myofibril• Location: around Z line – 1/sarcomere

° Open to extra cellular compartment -lined by external lamina

° Ø 2.5 X T tubule in skeletal muscle• Function: facilitate conduction – depol. wave -along

sarcolemma• Associated with sarcoplasmic reticulum: T tubule +

small terminals dyad

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Myofibrils• A band (dark) – H band (light) – M line• I band (light) – Z line (Z disk, dark)• Sarcomere = myofibril region between 2

Z line = 1 contractile unit• Contraction:

° I band - shortened° H band - disappeared° A band - constant° Z line - approaching each other

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Cardiac muscle fiber-atrium• Ø < fiber in ventricle myoendocrine cells• Contains granules - cardiodilatin (CDD)/Atrial

Natriuretic (Poly)peptide (ANP) – esp. in right atrium ° ANP – regulation of fluid –electrolyte balance

• Efferent arteriole constriction diuresis, sodium excretion↑

• Sodium, water resorption in kidneys (renal tubules)↓ blood pressure ↓ -

• Vasodilatation

• inhibit the release of arginine-vasopressin (posterior hypophysis), and aldosterone (adrenal cortex)

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Skeletal muscle• investments

° Epimysium – muscle – irregular dense collagenous connective tissue

° Perimysium – fascicles (bundles) - < dense° Endomysium – muscle fiber (cell) - reticular

fiber, basal lamina / external lamina

• cell° Skeletal muscle fibers – striated – parallel° Satellite cells

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Skeletal muscle cells/fibers

• Development: myoblast – parallel end –end fused myotube – formed myofibril skeletal muscle fiber

• Shape: long, tubular – Ø 10-100μm

• Between fibers: endomysium + continuous capillaries – parallel to fiber

• Skeletal muscle fiber – non branching -striated - multinucleated

• Nuclei – periphery – in a row – inside cell membrane (sarcolemma)

• EM: Sarcolemma invaginate T tubule (transverse tubule)

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Sarcoplasm: contains• A lot of myofibril Ø-1-2 μm –longitudinal – along

the fiber – regularly arranged striation in longitudinal section: ° A band – (anisotropic on polarized light dark) ° I band– (isotropic on polarized light light)

• EM: Sarcoplasmic reticulum = smooth surface endoplasmic reticulum ° Form a network around myofibril° Function: intracellular Ca storage (esc. terminal cysterna)° A-I junction – dilated terminal cysterna

• The membrane has junctional feet (= voltage gated Ca release channels)

° The rest = longitudinal sarcotubules + their branches

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T tubule• Tubular invagination –transversal – branching-

anastomosing – intertwine among myofibril• Location: transversal plane - A-I junction 2 in

each sarcomere• To extra cell - open• Associated with sarcoplasmic reticulum• Function: facilitate conduction of depol wave

along sarcolemma• T tubule + 2 terminal cysternae triad

° function: spreading of depol wave – fast – from sarcolemma – trough out the cell – to terminal cysterna

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Jeanne A Pawitan

Myofibril • A band (dark) – H band – pale –M line• I band (light) –Z line, Z disk – thin, dark• Sarcomere = myofibril area between 2 Z line =

contractile unit of skeletal muscle fiber• Contraction:

° I band shortened

° H band disappeared

° A band remain unaltered

° Z line – move closer together

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Satellite cells

• Satellite cells = regenerative cells

• Small cell – location: shallow depression – muscle cell’s surface

• External lamina – shared with muscle cell → inside external lamina

• Nucleus-one - > dense - > coarse

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Myotendinuous junction

• Connective tissue–muscle – tendon – continuous° Cells tapered – fluted (deeply folded)° Collagen fibers-tendon – penetrate

• Infoldings

• Endomysium – continuous – reticular fibers

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Innervation of skeletal muscle• Motor nerve fibers (α motor neurons –axon-

myelinated) branching – unmyelinated (Schwann cells +) – terminal dilated - myoneural junction (motor end plate)° Axon terminal° Synaptic cleft° Muscle cell membrane

• Sensory nerve fibers ° muscle spindles – among muscle cells –stretch Rx° Golgi tendon organ (neurotendinuous spindle)–

inhibitory feedback - α motor neurons - relax

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Regeneration - muscles

• Skeletal muscle – regeneration (+)° Skeletal muscle fiber ≠ mitosis° Satellite cells

• Injury: satellite cells - mitosis – hyperplasia• At muscle building: satellite cell – muscle fiber -

fusion mass increase hypertrophy

• Cardiac muscle - ≠ regeneration, fibroblast – connective tissue (scar)

• Smooth muscle – regeneration (+)

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Regeneration – smooth muscle

• Injury formation of new fibers° Mitosis – smooth muscle fiber (GI tr., urin. tr.)° Differentiation - pericyte – blood vessel

• Uterus –pregnant – smooth muscle° hyperplasia - mitosis° hypertrophy

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Nervous tissue

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Neurons • Cell body (soma,

perikaryon) – nucleus –nucleolus prominant

• Dendrite (multiple) ° Nissl bodies

° Branching

• Axon (single) – long - branching° Axon Hillock

° Axon terminals, end bulbs, terminal boutons → synapse

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Specialized cells

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Specialized cells

• Protein secreting cells

• Steroid secreting cells

• Neuroendocrine cells

• Cells in organs → other modules

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Protein secreting cells• Ex.: chief cells (stomach),

acinar cells (pancreas)• Shape: columnar,

truncated pyramid, etc• Basal cytoplasm -

basophilic° Nucleus° Rich in RER, polysome

• Apical cytoplasm - acidophilic° Secretory granules –

proenzyme (zymogen)

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Steroid secreting cells

• Ex: spongiocytes (adrenal cortex)

• Shape: polyhedral• Cytoplasm

° Extensive network of SER

° Lipid droplets – appear vacuolated

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Neuroendocrine cells

• Argentaffin, argyrophilic – silver staining

• APUD= amine precursor uptake decarboxylation

• DNES= diffuse neuroendocrine system

• Location: epithelium/glands – systems

• Secretory granules –at basal cytoplasm/ near blood vessel

Jeanne A Pawitan

Jeanne A Pawitan