Lecture B2 Flashcards by Tami Ojewole

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

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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

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Following gastrulation, the skin epidermis develops from ______

-single layer of ectoderm

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ectodermal progenitors forms epidermis under the influence of _____ (TFs) which does what?

-Wnt,BMP
-inhibits the response to FGF

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ectodermal progenitors undergoes neurogenesis under the influence of _____ (TFs)

-FGFs, BMP inhibition, absence of WNT

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FGF stands for ?

fibroblast growth factor

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embryonic epidermis undergoes parallel division under the influence of ______ to form _______ (layering of skin)

-BMPs, Notch
-stratified epidermis

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hair: embryonic epidermis under the influence of ______ forms _______

-Wnt
-Hair placodes (invaginations into CT to form hair follicle)

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epidermis of hair placodes is under the influence of ____

Wnts, EGF

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dermis of hair placodes is under the influence of ____

BMP inhibitors, FGFs

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3 layers of skin

-epidermis (most prevalent)
-dermis
-subcutaneous layer

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epidermis ( ____ origin) consists of _______

-ectoderm
-multiple layers of keratinized stratified squamous cells

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dermis ( ____ origin) consists of _______

-mesoderm
-CT, blood vessels, protein fibres (collagen), nerves

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subcutaneous layer (aka ____ ) is _______ + function?

-hypodermis
-loose layer of CT containing pads of adipocytes
-bind skin loosely to underlying tissue (muscle)

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epidermal cells receive nutrients from and release their wastes into ______

the areolar CT layer

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Hair follicle & Sebaceous layer are in this layer of skin?

dermis

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in the skin, epidermal ridges do what?

invaginate and interdigitate/interconnect with dermal papillae to increase the strength of both layers

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areolar CT does what?

-binds epithelial tissue to underlying tissues
-reservoir of water/salt

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thickness of skin

75-150 um

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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

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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

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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

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Keratinocytes move from _____

basal layer upwards to surface

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other cells present in skin

-melanocyte (pigment producing cells)
-langerhans cell (antigen presenting cells
-merkel cell (low threshold mechanoreceptors)

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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