AG RO Flashcards
What are the differnt modalities of stem cell division?
Asymmetric: most common, one of the two daughter cells remains a stem cell and the other moves towards differentiation.
Symmetric: one stem cell divides in either 2 stem cells or two differentiated cells.
These modalities may coexist in the same niche based on different physiological conditions.
How is stem cell division regulated?
Intrinsic: a cell polarity is defined due to the segregation caused by intrinsic determinant factors inside the cell.
Extrinsic: Signals from inside the niche promote self renewal or repress differentiation.
What is the difference between totipotent, pluripotent and multipotent stem cells?
Totipotent cells for example are those in the early stages of embryo development, they give rise to all cells in the embryo as well as extra embryonic cells. Pluripotent cells for example are Embryonic Stem cells bc they can give rise to all embryonic cells but not extra embryonic. Finally Multipotent cells are those that can develop in a limited number of cells found in a specific tissue such as Keratinocytes that give rise to nervous tissue cells.
What are some examples of post natal stem cell niches?
Crypts of the intestine, hair follicles, bone marrow and nervous tissue. The first two are more anatomically defined niches unlike the last two.
What is Somatic Cell Nuclear Transfer?
SCNT is when you take a nucleus from differentiated somatic cell - a mammary cell - and transfer it into the cytoplasm of an egg. Of course before that you must remove the nucleous of the oocyte. The last step is to implant the egg inside a recepient mother and technically - this is not 100% efficient - she will birth a clone of the donor. This proves that the differentiated somatic cells contain the genetic information of the whole organism.
How is reprogramming somatic cells into induced pluripotent stem cells done?
In this experiment they started by selecting 24 genes that qualified as possible factors that induced pluripotency in somatic cells. They inserted these genes one by one in cells with a cocktail of different TFs in a mouse fibroblast. They discovered that the cells obtained were very similar to ES colonies. They eventually were able to narrow down the number to 4 TFs and 4 genes that were very efficient in inducing PSCs.
What are the four main types of tissues present in our bodies?
Connective Tissue, Epithelial Tissue, Muscle Tissue, and Nervous Tissue.
What are some main characteristic of epithelial tissue?
This tissue covers all body surface, lines hollow organs and forms glands. It is very distinctive. It is polarized which will help distinguish apical, lateral and basal domains. It doesn’t have vessels so they are avascularized. There are very active stem cells that allow high turnover of the cells.
What are some main characteristic of connective tissue?
Less cells and more ECM and fibers. ECM is composed of ground substance with proteins, glycoproteins. The main cell is called fibroblast. Provides overall structural support and metabolic support to all tissues and organs.
What are some main characteristic of the nervous tissue?
Its main functions are that it detects, collects and analyzes stimuli from the environment. This tissue is soft, jelly like consistency. We are able to distinguish a grey and white matter.
What is H&E staining?
Hematoxilyn and Eosin staining is commonly used in histological samples. H which has a bluish/purple color stains nucleic acids and E which has a pink color stains proteins.
What is immunofluorescence?
We use an primary antibody that recognizes a specific molecules. Then we use a secondary antibody tagged with a flourescence tag that recognizes the primary antibody. Finally we use a flourescent microscope with a specific lamp to observe our target.
How are epithelia classified?
The epithilia can either be simple or stratified and can be squamous cuboidal or columnar. There are also other two special epithelia categories called pseudostratified and transitional.
All epithelia are classified based on their morphology not on function.
What are some main characteristic of simple squamous epithelia?
It is made of a single layer of flat scale-shaped cells. Most commonly found lining blood vessels and body cavities. It allows materials to pass through diffusion and filtration. Lines for example the bowman capsule in the kidney, alveoli of the lungs and a part of the cornea.
What are some main characteristic of simple cuboidal epithelia?
It is a single layer of cube-like shaped cells, mainly found in duct and secretory portions of the small glands.
What are some main characteristic of simple columnar epithelia?
Single layer of column shape cells, found mainly in ducts of many exocrine glands. The main function is secretion but also absorption. It can also be protective.
What are some main characteristic of columnar pseudostratified epithelia?
The nuclei are not aligned. Main functions are mucus secretion, found in the trachea, much of the upper respiratory tract, duct deferens.
What is epithelial metaplasia?
It means the conersion in post natal life of one cell type to another. For example going from pseudostratified columnar to stratified squamous. This conversion is used to adapt to the stress caused by the environment.
What is cell polarity?
Cell polarity indicates the different domain a cell has. The apical domain is the part of the cell that faces the lumen it may support structures like microvilli, stereocilia and cilia. The lateral domain faces the lateral part of the neighboring cell and supports junctions that keep the cells together. The basal domain is is the part below of the cell, it acts as a filter controlling the movement of substances with the CT below.
What are Occluding/Tight junctions?
They keep cells together like a zip. The zonula occludens is the region of contact between the two cells. Proteins like occludins and claudins help create the structure that keeps them together.
What are Anchoring/Adherent junctions?
They are beneath the tight junctions and they function in an area called zonula adherens. They aswell anchor cells together. The cell adhesion is mediated by proteins called cadherins. Desmosomes, hemidesmosomes and focal ashesion are some examples of anchoring junctions. The difference is that the last two anchor the basal domain of the cell to the basal lamina.
What are Gap junctions?
They are specialized intercellular connection between cells. They are formed by two hemichannels called Connexons, one provided by each cell. They aid the movement of small molecules, proteins , nucleic acids and sugars. They play key roles in many tissues such as heart, blood vessels, CNS and respiratory tract.
What are the basement membrane and the basal lamina of a cell?
The basal lamina is a fine extracellular layer, the basement membrane is the entire structure beneath the epithelial cells. The basement membrane has three distinct layers; lamina lucids which is electron lucent, lamina densa which is electron dense and lamina reticularis which is associated with retivular fibers of the underlying CT.
What are the two main types of glands? What the three types of secretion?
Exocrine: retain continuity with the external environment through ducts.
Endocrine: looses direct continuity with the external environment during development.
Merocrine: product is released through exocytosis. The gland can be either serous or mucous.
Holocrine: the whole cell ruptures releasinf the product
Apocrine: product released in the apical portion surrounded by thin cytoplasms and membrane.
What is Mesenchyme?
It is embryonic tissue found in the embryo. All CTs and other tissues derive from this tissue. They are considered multipotent stem cells. Even in adults we can find some niches of mesenchymal stromal cells and they are though to be like stem cells in adult tissue.
Why is ECM important and what are some of its features?
ECM provides pathway for cell migration, pathway for cell signaling and it senses the biochemical mechanical changes that occur.
How is connective tissue classified?
CT is classified based on the composition, organization of ECM and function. We have the Embryonic CT which contains the Mesenchyme and Whartons jelly - CT proper which is divided in loose and dense - and specialized CT such as cartilage, blood, bone, hematopoietic tissue, lymphatic tissue and adipose tissue.
What is the difference between an active and quiescent fibroblast?
Active: Active in the process of producing and secreting the ECM.
Quiescent: Not active in this process.
What is the difference between Blasts and Cytes?
A -blast every cell type in active state of proliferation and production and -cyte to every cell that is not active.
What are adipocytes?
They are cells found in the specialized CT of the adipose tissue. They derive from the mesenchyma and there are two types.
White: specialized in the storage of triglycerides and the main function is the storage of energy. Also involved in the synthesis of some hormones and GFs.
Brown: brownish color given by the mitochondria present, the main function is thermoregulation. They are abundant in infants and in mammals that hibernate.
Adipocytes are resident cells.
What are Mesenchymal stromal cells?
They are multipotent cells present in several adult tissues like bone marrow and adipose tissue. They can self renew, proliferate and differentiate in different tissues. They are probably remnants of mesenchymal cells and the most logical origin is the mesoderm.
What are the different connective tissue fibers?
Collagenous fibers, Reticular fibers and Elastic fibers.
What are collagen fibers?
Most common protein in the ECM and it is composed of glycine and hydroxyproline. Structurally three alpha chains wrap around eachother. Then they associate to form fibrils and then fibers. The synthesis starts in the RER and then they pass through the golgi for glycosylation. Histologically speaking you can see the nuclei of the fibroblasts.
Defects of collagen synthesis can cause diseases such as scurvy.
What are reticular fibers?
Composed of mainly type III collagen. They do not form bundle fibers but form a network that serves as a scaffold for all cells.
What are elastic fibers?
They are thin fibers compared to the other fiber types. They contain elastin. They also form a network. Produced by fibroblast but also muscle cells.
What are some features of muscle tissue and what are the different types?
Contractility is a fundemental property of muscle tissues. The contraction is performed by the sliding interaction of thick myosin filaments along thin actin filaments. The three main muscle tissue types are; skeletal, cardiac and smooth muscle.
Specific terminology is used when talking about the muscle cells; Cytoplasm is called Sarcoplasm - Smooth ER is called Sarcoplasmic Reticulum and the membrane and its lamina is called Sarcolemma.
The muscle tissue derives form the mesoderm.
What are some features of skeletal muscle tissue?
The fibers can be very long like in the arm or leg, but also very short like around the eye.
What are the stages of skeletal myogenesis?
During the embryonic stage there are inactive cells called Myoblasts, they will migrate and then fuse to become Myocytes. These primary myocytes fuse to give rise to myocytes which are multinucleated. Subsequently there is the formation of the basal lamina and the innervation.
What are satellite cells?
They are part of the myoblast that will fuse to give a multinucleated cell.
How is the skeletal muscle organized?
From the outside to the inside:
Muscle fibers are wrapped by a CT called deep fascia, then we have the epimysium. Next we have bundle of fibers called fascicles seperated by a layer of dense irregular CT called Perimysium. The next we have budles of muscle fibers surrounded by the Endomysium and finally we have the myofibrils.
What is the structure of the muscle fibers?
The sarcomere extends from one Z line to the other, it is symmetrical. The A band in the sarcomere is formed by myosin filamets - dark bands - and the I band is formed by actin filaments - light bands. The I bands are divided by the Z bands.
T tubules are invaginations in the sarcolemma and they are associated with two terminal cisternea of the sarcoplasmic reticulum, this structure is called Triad. This is the functional unit that is responsible for calcium release.
How does muscle contraction work?
An action potential in the motor neurons release Acetylcholine which binds to the nicotinic receptors of the muscle fibers which in turn cause a depolarization. This allows the calcium ions to enter the muscle fiber. Ca binds to Troponin which exposes the myosin heads which then can bind to the actin filaments. ATP is hydrolyzed and the release of ADP and P cause the myosin head to change position and cause the movement of the actin filament. This sliding of the filament causes a change in length - contraction.
What are the different types of muscle fibers?
Type I : Aka slow oxidative, mainly rely on aerobic metabolism, they contain mitochondria and capillaries. Also contain myoglobin. They are responsible for slow contraction over time.
Type II B : Aka fast glycolitic fibers have very few mitochondria and capillaries and mainly depend on anaerobic metabolism. They appear whitish and are responsible for the fast and short term contractions.
Type II A: Aka fast twitch oxydative, physiological and histological features intermediate between the other two types.
What is the gross morphology of the CNS?
Not a lot of CT, the tissue is very soft almost jelly like. It is possible to distinguish a grey and white matter.
How does the nervous system develop?
It develops early in the neural plate, from an invagination called the Neural Groove which generates the Neural Tube. At a certain time the cells from the neural tube detach and give rise to the Neural Crest cells which originate part of the PNS and other cell types. Cell types such as neurons, astrocytes and oligodendrocytes derive from the ectoderm of the neural tube.
What are neurons?
There are about 100 billion neurons which account for about 10% of total brain cells. Neuron is composed by a cell body, an axon and a dendrite. Mature neurons are not mitotically active, as of now neural stem cells are still under question. Multipolar neurons have one axon and a dozen dendrites and are the most common. Bipolar neurons have one axon and one dendrite and are found in the retina and olfactory mucosa. Pseudounipolar neruons are T shaped, and have a single short process that functions as an axon. Based on connection and function we can distinguish motor neurons, sensory neurons and interneurons.
What is a synapse and how does it work?
It is the site where one neuron transmits info in the form of an electric impulse to another target cell. The chemical synapse relies on the secretion of neurotransmitters in the space between the two cells called synaptic cleft. The binding of the neurotransmitter causes conformational chnage and the opening of a channel. The electric synapse makes use of gap junctions which align and allow the movement of small molecules and ions. They are faster but less specific.
How does the action potential work?
The resting potential is characterized by a greater concentration of ions outside the cell, when ions move inside the membrane depolarization occurs. Voltage gated calcium channels opens and allow calcium to enter the membrane causing depolarization. This causes the release of neurotransmitters which then bind on the postsynaptic membrane. Ligand gates ion channels are then opned resulting in the repolarization of the membrane.
What are some neurotransmitters and their functions?
Each neuron releases on type of NT. Acetylcholine is important in cognitive memory and movement, its dysfunction is associated to alzheimers and huntigtons disease. Dopamine is involved in reward, motivation, and motor function and is associated with parkinsons disease. Seratonin is involved in mood, memory processing, sleep and cognition.
What is the neuro muscular synapse?
It is the junction between a muscle fiber and an axon of a motor neuron. Two molecules of Ach bind to a nicotinic AchR.
What are astrocytes?
They have a star shaped morphology and many branches, they can be found both in gray and white matter. They retain the ability to proliferate. They regulate synapse info, elimination and function - they participate in the formation of the BBB.
What is the Blood Brain Barrier?
The BBB serves to prevent the migration of cells and other large molecules from the blood to the CNS. It is a specialized neurovascular unit evolved to maintain homoestasis, it is formed by endothelial cells connected to tight junctions surrounded by a basal lamina. It is highly selective semipermeable membrane, it also protects the brain from pathogens. Non-lipophilic molecules are not able to pass and this is of clinical relevance when dealing with drugs.
What are oligodendrocytes?
They are branched cells with many processes which are found both in white and gray matter. One of the main characteristics is that that it is very hard to see the nucleus. They are myelinating cells in the CNS. In gray matter they are poorly myelinated unlike in white matter.
Which are the myelinating cells of the PNS?
Schwann cells
What are microglia?
They are resident macrophage like immune cells of the CNS, they account for 5/15% of brain cells. They proliferate inside the tissue. They are very plastic and can undergo changes of shape in order to adapt to various needs. They are critical regulators of the CNS development and homoestasis. Since they are able to change their genetic signature they are really difficult to mark and detect. From their “ base “ shape - small body with many branches - they change shape retracting the branches so to be more motile.
What are ependymal cell?
These cells form the Ependyma which is a thin epithelial lining of the ventricular system of the brain and the spinal cord. They are similar to the mucosal epithelium and their main roles are protections, regulation of CNS and production of CSF.
What is the cerebro spinal fluid?
It is an aqueous solution with Na+, K+ and Cl- with very little proteins and few cells. It fills all the cavities of the CNS and has the function of protection from shocks and other types of damage.
What is the PNS?
The PNS consists of nerves and ganglia that reside outside the brain and spinal chord. There are three types of nerves: Afferent ( sensory ), Efferent ( motor ), and Mixed ( both sensory and motor ).
What are the two categories of astrocytes?
Protoplasmatic: They serve as transporters of nutrients and act as a barried. Found in gray matter.
Fibrous: Respond to injury and facilitate neural remodeling.
What is the choroid plexus?
It is a highly vascularized tissue located in the brain ventricle. It is a folded tissue which projects into the ventricles. It removes water and blood, also it helps produce CSF.
What is the function of the skin and what are the different layers?
The skin is the largest organ in our body. It is divided in Epidermis which is epithelium, Dermis which is the CT and Hypodermis which is loose CT, adipose tissue and vessels. Its functions are protection from the outside environment, sensory function bc of sensory receptors and mechanoreceptors, thermoregulation, and metabolic function.
What are the layers of the epidermis?
Starting from the dermis and moving outwards:
Statum basale, stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum.
Also, if the skin has the stratum lucidum it is defined thick skin, if it lacks it it is considered thin skin. Another difference between them is that the stratum corneum in the thick skin is much thicker compared to the thin skin.
The epidermis is not vascularized, all the nutrients come from the dermis.
What are some characteristic of the layers composing the epidermis?
Stratum basale: Single layer of cuboidal and columnar cells, we also have the presence of melanocytes and innervated Merkel cells which are responsible for sensing light touch.
Stratum spinosum: Spiny appearance due to the extension of the desmosomes. Cells have a polyhedral shape, they actively produce keratins. Contains langerhans cells which are fundemental for immunity.
Stratum granulosum: Flattened cells, composed of 3 to 5 layers of these cells. We find lamellar granules which contain lipids and glycolipids.
Stratum lucidum: Found only in thick skin, composed of flattened keratinocytes. No nuclei.
Stratum corneum: Can be made up of up to 20 layers of squamous flattened dead cells filled with keratins. Every two weeks the layers are sheded.
What is the structure of the dermis?
It is the layer beneath the epidermis, it is made of CT. The connection between the dermis and epidermis is very irregular. Dermal Papillae reinforce this junction. In the dermis we find innervation and vascularization. The dermis can be divided into Papillary dermis and Reticular dermis. The first is where the dermal papillae are found, the latter is in contact with the subcutaneous tissue. In the dermis two different types of plexuses can be found. The subpapillary plexus with venules and arterioles. The cutaneous plexus found in between the dermis and hypodermis which has veins, arteries and lymphatic vessels.
What is the structure of the hypodermis?
It is also called the subcutaneous layer or superficial fascia. It is no longer considered part of the skin. It is composed of loose CT and many adipocytes which act as fat storage, insulators and protectors from mechanical stress,
What are the different receptors and how is the skin innervated?
There are two categories of receptors in the skin: Free nerve ending and Encapsulated mechanoreceptors. The first are non capsulated and may have contact with merkel cells. The latter includes Pacinian corpuscule, meissner corpuscule, ruffini endings and krause end bulbs.
What are some appendages of the skin?
Sweat glands, sebaceous glands, hair follicles and nails. They all come from the down growth of epidermal cells into the dermis during the development of the organism.
What are sebaceous glands?
They are in close contact with the hair follicle and they discharge their product in it. It uses holocrine secretion, the cells break and release the content called the Sebum which is a mixture of lipids and lubricates the hair follicles.
What are sweat glands?
The most abundant sweat gland is the Eccrine sweat gland. It is tubular coiled exocrine gland. There is a duct which secretes sweat outside. Sweat is composed of water, salts and lactic acid. The Apocrine sweat glands are less common and only present in specific parts of the body, like the perineal regions. They mature around puberty and it secretes a milky protein rich serum.
What are hair follicles?
The three main parts are the Bulb which is the terminal part inserted into the dermis and epidermis, the Root which is the intermediate part in which we have the growth of the hair and the Shaft the external part of the hair.
