Lec 2 - Stem Cells and Differentiation

What is the difference between cell proliferation and cell differentiation?

Cell proliferation is the growth of a cell that contributes to the growth of organs, including cell replacement and growth.

Cell differentiation involves the renewal and specialization after creation from a stem cell.

How do embryonic stem cells and adult stem cells differ?

Embryonic stem cells can proliferate rapidly and have the ability to differentiate into all cell types in an organism, meaning totipotent.

Adult stem cells only differentiate into various cells of a specific lineage, being multipotent or even unipotent

What stage of the cell cycle are adult cells typically in? What is another word for this?

G0; quiescent cells

What are the differences between totipotent, pluripotent, multipotent, and unipotent stem cells?

Totipotent: have the potential to develop into a complete organism, including supportive tissues

Pluripotent: have the potential to become any of the germ layers

Multipotent: lineage committed cells with potential to give rise to all cells of the germ layer

Unipotent: committed cells that give rise to only one cell type

What are induced pluripotent stem cells?

Adult stem cells that have been reprogrammed by introducing extra copies of genes that control pluripotency.

What are the two classes of cells based on proliferative (growth) potential?

Resting/Quiescent cells (mitotically inactive but can resume)

Postmitotic cells: left cell cycle and are incapable of cell division individually (like perma G0; ex, neurons, cardiac and skeletal muscle, mature WBCs, and RBCs)

NOTE: hematopoietic cells are postmitotic, but are renewing via stem cells in bone marrow and whatnot

What is the result in gene expression changes in cells of a specific lineage?

Cells are committed to a specific lineage. This generates progenitor cells of a particular tissue (only able to repopulate the specific cells of that tissue)

Name some examples of places from which one can find post-mitotic cells in a human adult?

(cells that have permanently exited the cell cycle and are no longer capable of dividing)

Some examples include brain neuronal cells, skeletal muscle, cardiac muscle

Name some examples of places from which one can find renewing cells in a human adult?

Hematopoietic cells (blood cells and such) are constantly renewing

Name some examples of places from which one can find minimally committed adult stem cells in a human adult?

Bone marrow (make hematopoietic cells), testis (sex cells), intestines (intestinal epithelial cells are constantly turned over), skin (same reason as intestine), and hair follicle (duh)

What are some examples of mesenchymal stem cells? What does this mean?

MSCs are multipotent non-marrow tissues.

Some examples include, cartilage (chondrocytes), bone (osteocytes), tendon/ligament (fibroblasts), fat (adipocytes), marrow (stromal cells), CNS (astrocytes), skin (fibroblasts), and muscles (myocytes)

What are the three possible outcomes of cell division?

Symmetric stem cells (2 new same cells), Symmetric committed cells (2 new same cells but not stem cells), and asymmetric (1 stem cell + 1 committed cell)

What determines if cell division is symmetric or asymmetric?

The plane of division. This can either split the apical and basal membrane of the mother cell directly in half, OR it can split the basal membrane into one daughter, and the apical membrane into another

What are some extrinsic factors that control stem cell committment?

Extrinsic factors include chemical signals and physical environment.

Some chemical signals include growth factors and hormones.

Some physical environment features include the substratum (i.e. basement membrane), extracellular matrix, and cell-cell adhesion (like in cell plate cultures).

What are some intrinsic factors that control stem cell committment?

Intrinsic factors include genetic, epigenetic, and proteins (those that dictate cell polarity, as on apical and basal membranes)

How do extrinsic and intrinsic asymmetry differ?

As mentioned, extrinsic asymmetry is affected by the cell's external environment, that being something like a basement membrane.

Intrinsic asymmetry is affected by the cell's internal environment, such as proteins on the apical or basolateral membranes that make it polarized.

What are some of the key reprogramming factors involved in reprogramming adult somatic cells?

Oct3/4, Sox2, Klf4, and c-Myc

What is another term for cellular reprogramming in terms of differentiation?

Transdifferentiation is the possibility that somatic cells can be reprogrammed into other types of differentiated cells

What are transit amplifying cells?

Stem cells that have committed to their pathway to differentiation, but have not become unipotent yet

Describe how and why intestinal epithelial cells are constantly renewing?

Stem cells exist at the bottom of crypts that create transit amplifying cells that travel to the surface of villi as old IECs are shed.

They renew because being a cell is hard :(

Also in order to permit gut health.

What is unique about liver epithelial cells?

They are normally quiescent, but are stimulated to proliferate if large numbers of liver cells are lost

What are the stem calls of adult muscle? When do they proliferate?

They usually hve little cell turnover, but regenerate from satellite cells (muscle stem cells) in response to injury.

What is the endoplasmic reticulum referred to in myocytes?

Called sarcoplasmic reticulum, in muscle cells, and the Ca2+ release and uptake is involved in muscle contraction

What do H&E stains do respectively?

Haematoxylin (H), is a blue dye that binds to negatively charged molecules, like DNA and RNA, because it stains basophillic (acidic) structures.

Eosin binds to positively charged mitochondria and stains them pink because it stains acidophillic (basic) structures.

What is metaplasia?

a switch that occurs in tissue differentiation that converts one cell type to another, altering its functional ability

What is a stem cell niche?

Microenvironment around stem cells that provides support and signals regulating self-renewal and differentiation

How is a stem cell niche maintained?

Integrin-mediated attachment (a protein that links a cell to its ECM) between stem cells and other cell types maintains a niche