CSB329H1 Lecture Notes - Lecture 6: Network One, Dystroglycan, Glycoprotein
9 May 2018
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Lecture 6(a): Stem Cells & ECM
• Knowledge about the ECM allowed to use the knowledge of stem-cell therapy leading to the
generation of organoids
o Organoids are a 3D
in vitro
tissue model that displays the physiological relevant features
of an organ; it must display realistic micro-anatomy
ð Multipotent intestinal stem cells (ISC)-derived organism culture system is a phenomenal model
because epithelial cells rapidly turn over requiring a stem-cell population
Stem Cell Niche:
1. Basal Lamina/Basement Membrane:
o Specialized extra-cellular matrix sheet that underlies epithelial cells – epithelial cells
are very sticky to the basal lamina; adhesive forces come into play
o Sheet like structure made up of 4 core components:
a) Laminin
b) Collagen IV
c) Nidogen
d) Perlecan
o Cells are not only adhesive but they are bound – receptors are involved which correlate
with a transduction event; stiffness of the matrix is dependent on cellular activities
§ Basal lamina is universal; no multicellular organism exist w/o a basal lamina
2. Interstitial ECM:
o Consists of collagen I – functions in the formation of spirals does not form sheets
§ Most abundant protein in the body that dictates organ shape; capable of
forming spirals in different polarities depending on the tissue
Basal Lamina:
• Universal Components:
o Nidogen, Perlecan, Laminin, Type IV Collagen, Integrin
ð Fibronectin is not part of the basal lamina but are found in our open circulatory system
Integrins:
• Integrins are major transmembrane cell surface matrix receptors
that function to interact indirectly with the actin cytoskeleton
o Once an integrins binds to an extracellular cell surface molecule (i.e. Laminin) it
functions to transduce the information intracellularly
• Integrins, independently, do not have enzymatic activity – cannot transduce a signal
o When integrins are found in clusters they are capable of transducing a signal
ð It is all coordinated: migrating cells bind to the ECM and use integrins as a primary cell matrix
receptor - which transduces the signal causing the actin cytoskeleton of the cell to remodel:
regulating the actin dynamics leading to a mechanical event
Unique biochemical
property of collagen is
tensile strength;
resistant to shear forces
Sense extracellular
environment via integrins
Document Summary
Multipotent intestinal stem cells (isc)-derived organism culture system is a phenomenal model because epithelial cells rapidly turn over requiring a stem-cell population. Basal lamina is universal; no multicellular organism exist w/o a basal lamina: interstitial ecm, consists of collagen i functions in the formation of spirals does not form sheets. Most abundant protein in the body that dictates organ shape; capable of forming spirals in different polarities depending on the tissue. Basal lamina: universal components, nidogen, perlecan, laminin, type iv collagen, integrin. Fibronectin is not part of the basal lamina but are found in our open circulatory system. Integrins are major transmembrane cell surface matrix receptors that function to interact indirectly with the actin cytoskeleton: once an integrins binds to an extracellular cell surface molecule (i. e. laminin) it functions to transduce the information intracellularly. Integrins, independently, do not have enzymatic activity cannot transduce a signal: when integrins are found in clusters they are capable of transducing a signal.
