Lecture 3: MSC-Derived Connective Tissue

Question 1

Mesenchymal stem cell

Answer 1

Progenitor for all resident tissue cells, differentiates from ESC

Question 2

Basic components of all connective tissue

Answer 2

1. Cells
2. Fibers
3. Ground substance

Question 3

Extracellular matrix

Answer 3

Composed of all extracellular parts of connective tissue (fibers + ground substance)

Question 4

Type II collagen

Answer 4

Primary part of hyaline cartilage. Very tight, hydrated ECM that makes cell motility impossible.

Question 5

Type I collagen

Answer 5

Dominant large fiber of CT. Forms ropes/sheets for structural and space-filling roles as procollagen linked into fibrils. More type I = more density

Question 6

Hydrogels

Answer 6

Bioengineered compounds that mimic CT properties

Question 7

Mesenchymal stem cell

Answer 7

Progenitor cell for all stromal cells of CT compartments (adipocytes, fibroblasts, muscle)

Question 8

Unilocular adipocytes

Answer 8

Also known as white fat cells occur in white adipose tissue and primarily act as energy storage. Will often undergo hypertrophy instead of dividing.

Question 9

Multilocular adipocytes

Answer 9

Also known as brown fat cells, occurring in brown adipose tissue. Specialized for thermogenesis.

Question 10

Beige fat cells

Answer 10

Transitional stage between from white fat to brown fat. Multilocular thermogenic cells found in white adipose tissue

Question 11

Fat depots

Answer 11

Areas of white fat collections, e.g. the subcutaneous, visceral, and intermuscular fat.

Question 12

Fibroblasts

Answer 12

Cells responsible for production, remodeling, and degradation of ECM fibers and ground substance

Question 13

Myofibroblasts

Answer 13

Myosin-producing fibroblast subtype. Responsible for generating force, e.g. in wound closure

Question 14

Type III collagen

Answer 14

Dominant small fiber of CT and in the mesenchyme (embryonic undifferentiated CT). Provides support in regions with more cells. More type III vs type I typically makes looser CT. AKA reticular fibers

Question 15

Elastin

Answer 15

Main protein in elastic fibers, along with some fibrillins. Provide stretchiness in CT.

Question 16

Type IV collagen

Answer 16

Forms the lamina densa of external/basement membranes

Question 17

Type VII collagen

Answer 17

Forms anchoring filaments in lamina reticularis of external/basement membranes

Question 18

Type X collagen

Answer 18

Supportive role necessary for deposition of type I collagen at bone growth plates

Question 19

Type V collagen

Answer 19

Necessary for fibrillation of type I and III collagens.

Question 20

Classes of fibrous CT

Answer 20

1. Loose
2. Dense irregular
3. Dense sheet-like
4. Dense regular

Question 21

Loose connective tissue

Answer 21

Contains a higher proportion of type III collagen and ground substance. Fibers have irregular orientation, fills layers that allow cell motility and also loose-cell-ball organs e.g. spleen, lymph nodes

Question 22

Dense irregular connective tissue

Answer 22

Mostly type I collagen arranged in 3 dimensions; default space-filling CT. Generally does not allow cell motility (but density is on a spectrum).

Question 23

Dense sheet-like connective tissue

Answer 23

Mostly type I collagen arranged in 2D sheets. Compartmentalization of CT like bones, joints - forms sheaths and fascia

Question 24

Dense regular connective tissue

Answer 24

Mostly type I collagen aligned in 1 dimension. Highly regulated development via other collagens and mostly only found in tendons/ligaments.

Question 25

Matrix metalloproteases (MMPs)

Answer 25

Class of compounds that degrade collagens, elastins, and other CT parts. Some are specific to collagen type.

Question 26

Ground substance

Answer 26

Occupies space between CT cells and fibers. Consists of highly hydrated proteoglycan complexes and glycoproteins

Question 27

Proteoglycan

Answer 27

Large molecule with backbone (e.g. hyaluronic acid), proteoglycan stems, and glycosaminoglycans (GAGs) with associated water molecules

Question 28

Peri-neuronal nets (PNNs)

Answer 28

EC proteoglycan structure that surrounds neurons. Guide/deter the growth trajectory of new axons and formation of new connections.

Question 29

Examples of glycosaminoglycans

Answer 29

Dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate

Question 30

Matrisome

Answer 30

The entire ECM of the CT in a given location

Question 31

Matrisome core components

Answer 31

1. ECM glycoproteins (non-fibrillar proteins) 2. Collagens 3. Proteoglycans 4. Associated proteins, regulators, secreted factors

Question 32

Cellular CT disorders

Answer 32

Often immune-mediated; e.g. immune responses can reduce the fibrous fraction and weaken CT walls

Question 33

Fibrous CT disorders

Answer 33

Fibroproliferative responses, e.g. cysts, loss of flexibility, keloid scars, organ LOF due to scarring. Some genetic fiber disorders e.g. Marfan

Question 34

Ground substance CT disorders

Answer 34

Imbalance of fluid flow can lead to edema. Caused by occlusion of fluid drainage or inadequate circulation.

Question 35

Uncoupling protein

Answer 35

UCP-1 determines if fat will be thermogenic; changes mitochondria product from ATP to heat

Question 36

CT origin

Answer 36

Mesoderm layer. After folding, mesoderm comes to fill space between ectoderm (outside) and endoderm (gut tube)

Question 37

Trans-differentiation

Answer 37

Conversion of one cell type to another, e.g. adipocytes <-> muscle <-> fibroblasts

Question 38

De-differentiation

Answer 38

Process by which cells become less specialized and return to earlier state in lineage, e.g. adipocyte/fibroblast/muscle -> MSC

Question 39

Adipocyte hypoxia

Answer 39

Adipocyte hypertrophy can outgrow oxygen supplies, leading to cell death and inflammation; may mediate many obesity-related disorders.

Question 40

Highly fluid CT

Answer 40

Blood and lymph are examples of highly fluid and cellular CT, low in fibers

Question 41

Highly fibrous CT

Answer 41

Tendons and ligaments are examples of highly fibrous CT, with low cells (and low cell motility) and lower ground substance

Question 42

Functional classes of collagen

Answer 42

1. Fibrillar (Type I, II, III) 2. Fibrillar anchoring (Type VII) 3. Meshwork (Type IV) 4. Other nonfibrillar (many)

Question 43

External membrane

Answer 43

Membrane that surrounds adipose and muscle tissue

Question 44

Basement membrane

Answer 44

Membrane on basal side of epithelia (always have polarity). External = basement when epithelium is attached.