Stem Cells and Tissues Quiz

BIOS 367 Cell Biology, Fall 2024, Chapter 22 Part 1

• Stem Cells in Tissue Homeostasis and Regeneration: Tissue homeostasis is like a river, with new cells flowing in and differentiated cells flowing out, maintaining dynamic equilibrium.
• Tissue Homeostasis: A constant flow of new cells, generated by cell division, and a constant loss of differentiated cells, due to normal turnover or injury, create a dynamic equilibrium.
• Epidermis Example: The epidermis, a type of epithelial tissue, demonstrates this. Dead cells are sloughed off, while new epidermal cells mature and push up from underneath. Mitosis is frequent in the lower layers, generating new skin cells.
• Stem Cell Defining Characteristics: Stem cells can either remain a stem cell, during self-renewal, or commit to differentiation after multiple divisions. Stem cell self-renewal maintains the stem cell pool within a tissue.
• Stem Cell Hierarchy: Stem cells, progenitor cells, and differentiated cells are arranged in a hierarchy. Tissue-specific stem cells produce progenitor cells that divide a limited number of times before differentiating. Different cells can be unipotent (produce only one type) or multipotent (produce multiple types).
• Gut Epithelial Lining Renewal: Stem cells in the gut epithelial lining exhibit a 3 - 5 day transit time from the crypt to the villus. Specific G-protein coupled receptor Lgr5 is expressed in these stem cells. Rapidly dividing cells have a 12-hour cycle time. Nondividing differentiated cells make up the villus.
• Four Main Differentiated Cell Types in Small Intestine: Absorptive, goblet, Paneth, and enteroendocrine cells.
• Absorptive Cells: High number, microvilli provide a significant surface area to import nutrients and aid in the final stages of extracellular digestion.
• Goblet Cells: Secrete mucus, which covers the epithelium and provides protective coating.
• Paneth Cells: Secrete cryptdins (defensins) to kill bacteria and some growth factors.
• Enteroendocrine Cells: Numerous subtypes, secrete serotonin and peptide hormones, affect gut wall neurons and regulate growth/proliferation/digestive activities.

Identifying Stem Cells

• Methodologies for Identifying Stem Cells: Stem cells are usually rare in adult tissues and challenging to identify in conventional tissue sections unless a specific marker is available. Recombinant DNA technology provides a powerful tool using cell lineage tracing.
• Cell Lineage Tracing: This technique uses transgenic animals to mark specific cells, and tracks their progeny, leading to a clonal lineage that includes stem cells and differentiated cells.

Recombination Methods

• CreERT2 System: Cre recombinase is inactive unless activated by tamoxifen. Adding tamoxifen activates the recombinase. In some cells, it removes a blocking sequence, leading to GFP expression.
• Stem Cell Label Example: If recombination happens within a stem cell, the labeling will remain consistent with time; if within another cell type, the label will vanish as the cell differentiates.

Muscle Repair

• Skeletal Muscle Repair: Skeletal muscle cells are long, multinucleated. Quiescent satellite cells proliferate and fuse with existing muscle cells when damaged or stimulated to grow. Satellite cells are a self-renewing source of terminally differentiated myoblasts.

Blood Cells

• Blood Cell Functions and Concentrations: Blood cell types, such as erythrocytes (red blood cells), leukocytes (white blood cells), monocytes, granulocytes (neutrophils, basophils, eosinophils), lymphocytes (B cells, T cells, and NK cells), and platelets, are presented with their concentrations and main functions in the human blood.

Bone Marrow Rescue

• Bone Marrow Transfusion: Injecting stem cells from a healthy donor into an irradiated mouse can rescue the mouse's blood cell production. A single blood stem cell can reconstitute the entire mouse hematopoietic system, producing differentiated blood cell types.

Hematopoiesis

• Hematopoiesis Scheme: A simplified scheme of mouse/human blood cell development (hematopoiesis). Stem cells, multipotent progenitors, and committed progenitors are shown with their differentiation pathways into mature blood cells.

Stem Cell-Free Tissues/Examples

• Tissues that Do Not Require Stem Cells: Some tissues, like pancreatic beta cells and hepatocytes, can regenerate without stem cell involvement due to division abilities of fully differentiated cells.
• Tissues Lacking Stem Cells: Examples of tissues without active stem cell populations and incapable of regeneration, such as auditory epithelium and retinal photoreceptors

Stem Cell Identity

• Signalling Molecules (Niches). Stem cells maintain identity within specialized microenvironments (niches). Signaling molecules from supporting cells or extracellular matrices concentrate within the niche. Niche-supporting environments can be small, and some cells within a short distance from a niche can still engage in self-renewal.

Lgr5-Related Minigut Processes

• Cultivation of Lgr5 Expressing Cells: A single Lgr5 expressing cell within a cell-free matrix produces a minigut over time. Differentiated Paneth cells will emerge from certain cells; these secrete Wnt proteins that maintain Lgr5 stem-cell expression in neighboring cells.

Stem Cell Niche: C. elegans Gonad

• Distal Tip Cells in C. elegans Gonad: The distal tip cell in the C. elegans gonad plays a key role in the stem-cell niche. Distal tips of the cell extend across multiple stem-cell diameters to maintain stem-cell identity through Notch signaling, which is cell-contact dependent. Cells detach from the distal tip and go through meiosis, producing eggs or sperm.

Asymmetric/Symmetric Divisions

• Asymmetric vs. Symmetric Divisions: Asymmetric stem-cell divisions result from a cell-fate determinant that is localized to one side of the cell. Only one daughter cell inherits this determinant and remains a stem cell; the other undergoes differentiation. Symmetric stem-cell divisions result in both daughter cells inheriting determinants and remaining as stem cells. These two division models are visually depicted.
• Plane of Division in Drosophila Testis: The plane of division of germ-line stem cells in the Drosophila testis is a critical determinant for which daughter cell maintains contact with the niche. The daughter cell oriented so to remain in contact with the somatic niche retains the self-renewal capacity, while the other doesn't.

Independent Choices for Stem-Cell Daughters

• Environmental Influence: Daughter cells' choice of self-renewal or differentiation might depend on the local environment a daughter cell is exposed to.

• Stochastic Outcomes: In some cases, the choice is made randomly (stochastically), with potential outcomes including whether a daughter cell commits to differentiation or remains as a stem cell. Factors such as environmental conditions may influence this randomness.