Lecture B2 Flashcards
Our skin is the _____ in the human body (______ total body weight)
In adults: skin’s SA is _____
Renew skin every _____ depending on age
When older, renew skin every ____ depending on age
-largest single organ
-15-20%
-1.5-2 m^2
-20-30 days
-50-80 days
main functions of skin epithelia
-Protective – physical barrier
-Sensory - sensory receptors in the skin
-Thermoregulation – assists in maintaining constant body temperature
-Metabolic – produces Vitamin D3, energy stored in fat, remove electrolytes through sweat
Following gastrulation, the skin epidermis develops from ______
-single layer of ectoderm
ectodermal progenitors forms epidermis under the influence of _____ (TFs) which does what?
-Wnt,BMP
-inhibits the response to FGF
ectodermal progenitors undergoes neurogenesis under the influence of _____ (TFs)
-FGFs, BMP inhibition, absence of WNT
FGF stands for ?
fibroblast growth factor
embryonic epidermis undergoes parallel division under the influence of ______ to form _______ (layering of skin)
-BMPs, Notch
-stratified epidermis
hair: embryonic epidermis under the influence of ______ forms _______
-Wnt
-Hair placodes (invaginations into CT to form hair follicle)
epidermis of hair placodes is under the influence of ____
Wnts, EGF
dermis of hair placodes is under the influence of ____
BMP inhibitors, FGFs
3 layers of skin
-epidermis (most prevalent)
-dermis
-subcutaneous layer
epidermis ( ____ origin) consists of _______
-ectoderm
-multiple layers of keratinized stratified squamous cells
dermis ( ____ origin) consists of _______
-mesoderm
-CT, blood vessels, protein fibres (collagen), nerves
subcutaneous layer (aka ____ ) is _______ + function?
-hypodermis
-loose layer of CT containing pads of adipocytes
-bind skin loosely to underlying tissue (muscle)
epidermal cells receive nutrients from and release their wastes into ______
the areolar CT layer
Hair follicle & Sebaceous layer are in this layer of skin?
dermis
in the skin, epidermal ridges do what?
invaginate and interdigitate/interconnect with dermal papillae to increase the strength of both layers
areolar CT does what?
-binds epithelial tissue to underlying tissues
-reservoir of water/salt
thickness of skin
75-150 um
layers of epidermis in thin skin from top to bottom (not in palms and soles) + function
-Stratum corneum- dead cells with keratin that have lost nucleus and cytoplasm for (waterproof) protection
-Stratum granulosum- thin layer of cells to prevent fluid loss/layer between live & dead cells, secrete lameller bodies
-Stratum spinosum- living keratinocytes, synthesis of keratin, has a lot of desmosomes for anchoring, strength & flexibility, forms ridges
-Stratum basale- single cell (cuboidal/columnar) layer, highly mitotic (stem cells), basal layer
thin skin vs thick skin
-Dermis of thin skin more cellularized and well vascularized than in thick skin
- Thin skin contains more elastin and less coarse bundles of collagen
-Thick skin epidermis is thicker
layers of epidermis in thick skin from top to bottom (palms and soles) + function
-Stratum corneum- dead cells with keratin that have lost nucleus and cytoplasm for (waterproof) protection
-Stratum lucidum- thin layer of dead cells that only appear in thick skin
-Stratum granulosum- thin layer of cells to prevent fluid loss/layer between live & dead cells, secrete lameller bodies
-Stratum spinosum- living keratinocytes, synthesis of keratin, has a lot of desmosomes for anchoring, strength & flexibility, forms ridges
-Stratum basale- single cell (cuboidal/columnar) layer, highly mitotic (stem cells), basal layer
Keratinocytes move from _____
basal layer upwards to surface
other cells present in skin
-melanocyte (pigment producing cells)
-langerhans cell (antigen presenting cells
-merkel cell (low threshold mechanoreceptors)
stem cells of epidermis reside _____
in basal layer
only skin layer in thick skin
stratum lucidum
basal layer of epidermis attached via ____ to underlying basement membrane
-intergins
Secreted factors from dermal fibroblasts promote _____
the proliferation of the basal epidermal cells
_____ is one of the major cues directing skin development and maintenance
-Wnt signaling
Stem cells from basal layer that divide form _____
-Notch activated terminally differentiating cells which move up into other layers (NOTCH signalling increases)
Stem cells of epidermis on the tip of ____ divide ______
-dermal papilla
-infrequently and always in sideway direction
_____ is required to maintain epidermis
Wnt signaling
marker for skin stem cells
B1- subunit of integrin, Lgr6+
marker for skin differentiating cells/keratinoyctes
keratin 10
transit amplifying cells of skin are ____
short-lived
skin epidermis: differentiation increases as _____
you move up the skin layers
Factors of epidermal SC niche (4)
-secreted factors (Wnt, EGF)
-cell-cell contact
-ECM
-physical factors (elasticity, topography- shape of cells)
Rate of proliferation of epidermal SC layer is determined by _______
-signals (growth factors)
-direct cell-cell contact that come from the terminally
differentiated epidermal cells overlying the
stem cell layer
Importance of the niche in the epidermis was determined by _____
-autologous skin graft on severe burn patients
Hair follicles cycle through ______. Stem cells active when?
-bouts of hair growth and degeneration
-only periodically
part of hair follicle
-hair shaft (seen above the skin)
-infundibulum
-isthmus + sebaceous gland
-bulge
-hair germ
-dermal pailla (CT)
stem cell niche of hair follicle = ____ + ___
-bulge
-hair gem
Growth cycle of hair follicle
-rest (telogen)
-growth (anagen)
-regression (catagen)
stem cells in lower bulge can do what?
makes all the lineages of the hair follicle
Stem cells in the epithelia produces this TF to constantly proliferate to renew epidermis
-Lgr6+
Secondary hair gem TF
-Keratin: Krt15
-Gli1+
-Lgr5+
Wnt signalling
Hair Bulge TF
-Keratin: Krt15
-Cell surface: Cd34+, Lgr5+
-TF: Sox9+
Isthmus TF
-Gli1+
-Lgr6+
Sebaceous gland TF
-Blimp1+ (PRDM1)
-Lgr6 (for the development of gland)
Junctional zone (where follicle exits skin) TF
-Lrig1+
-EGF signaling
Interfollicular epidermis is the _____
epidermis between hair follicles
molecular identity of interfollicular epidermis (IFE) is ____
unclear
____ signalling is required for hair follicle induction
Wnt
____ signalling from nearby nerves to activate target Gli1
Shh
Epidermal lineage commitment with multipotent stem cells contributing to ______ (3)
-the epidermis
-the hair follicle
-the sebaceous gland (SG)
there is also a unipotent stem cell population in the sebaceous gland that are _____, which regulates ____ and governs activity of _____
-Blimp1 positive (PDRM1 positive)
-homeostasis of sebaceous gland
-Bulge SCs
sebaceous gland buds from the ______ as a terminally differentiating structure
-upper ORS (outer root sheath)
Sebaceous gland formation is regulated by ______ and produces _______
-Notch and Hedgehog signaling pathways
-lipid rich sebum
Proliferative sebocytes TF
Ki67+, Blimp1, K14,K5, C-myc
Differentiated sebocytes TF
PPARy+
Blimp 1 inhibits ___ in sebocyte progenitor
C-myc
Blimp1 SC are distinct from ____
multipotent SC pop’n
sebaceous gland turnover occurs continuously during _____
adult homeostasis
sebocyte creation
multipotent SC form isthumus & junctional zone
-sebocyte progenitor
-proliferative sebocyte/transit amplifying cells
-differentiated sebocyte (secrete sebum)
Krt15+ progeny of SC is _____? Lgr6+, Gli1+? Lrig1+? IFE?
-transient
-long-lasting
-longlasting
-longlasting
-longlasting
-Upon wounding HFSCs are able to migrate into _____.
If hair follicle stem cell pool (bulge stem cell niche) is
lost due to injury, ______ are induced to
enter and repopulate the niche. Plasticity needs ___ signalling
-the IFE to regenerate the epidermis and, vice versa
-IFE stem cells, HF progeny, infundibulum and sebaceous glands
-SHH
Genes in the ______ control orientation and differentiation of hair follicles. Generally hair is in the same direction along _____. Requires ____ signalling
-planar cell polarity (PCP) pathway
-the body axis or orient to form a whorl
-Wnt
Loss of HFSC niche in bulge as one ages leads to _____; young SC + old dermis = ___
young SC + young dermis = ____
balding
-no growth
-growth
Bioprinting (def.)
-advanced manufacturing platform that enables the predefined deposition of living cells, biomaterials, and growth factors using computer-aided design to fabricate customizable constructs via a layer-by-layer printing process with a high degree of flexibility and repeatability
bioprinting technique
-A skin biopsy is collected from the patient and cultured in vitro to obtain a sufficient amount of cells
-Bio-inks in the form of cell suspensions, hydrogels, or cell-encapsulated hydrogels are used to fabricate bioprinted skin constructs
-Printed construct is cultured under submerged conditions followed by an air-liquid interface to obtain mature skin suitable for transplantation
