Differentiation
First off, just a quick note about differentiation. The inner cell mass of the embryo has embryonic stem cells, which can differentiate into pretty much any cell of the body. Induced pluripotent stem cells can do the same. Throughout development, the ectoderm, mesoderm and endoderm form, along with slightly more mature cells, such as bone marrow-derived stem cells and adipose-derived stem cells (both from the mesoderm). These cells are more specific in what they will become later, but they are still fairly generalised (so if necessary, adipose-derived stem cells could become brain cells... I think). Eventually, these cells differentiate further into more and more mature cells.
Another quick note: there's a difference between progenitor cells and stem cells. Stem cells can become basically anything, whereas progenitor cells are pretty much destined to become only one type of mature cell (e.g. osteoblasts can become osteocytes).
Cardiac muscle
Cardiac muscle can be derived from cardiac stem cells, which in turn can be derived from bone marrow-derived stem cells or adipose stem cells, which in turn can be derived from embryonic stem cells (or induced pluripotent stem cells). Only a very small percentage of heart cells are cardiac stem cells, which is why the heart cannot repair itself after a myocardial infarction or other kinds of damage. Cardiac differentiation requires certain signalling pathways, such as the Wnt/β-catenin signalling pathway. When this pathway is knocked out, cardiac differentiation does not occur. (One marker that can tell you whether or not cardiac differentiation has occurred is Nkx2.5.)
Cardiac muscle, like every other kind of cell, has adhesions to the ECM and to other cells. Integrin and focal adhesion complexes are important for adhesions to the ECM, whereas N-cadherin and α/β cetanin are important for cell-cell adhesions. Cell-cell adhesions may be more important than cell-ECM adhesions in determining the stiffness of the cells.
When culturing cells in vitro, it is possible to detach them from the synthetic ECM without destroying cell-cell adhesions. This can be done by using a temperature-sensitive hydrogel which allows for spontaneous detaching when the temperature is decreased. "Sheets" of cells created in this manner can be stacked on top of each other (but only to a certain extent- if you stack too many sheets, the cells in the middle won't get enough nutrients).
Cardiac muscle, like every other kind of cell, has adhesions to the ECM and to other cells. Integrin and focal adhesion complexes are important for adhesions to the ECM, whereas N-cadherin and α/β cetanin are important for cell-cell adhesions. Cell-cell adhesions may be more important than cell-ECM adhesions in determining the stiffness of the cells.
When culturing cells in vitro, it is possible to detach them from the synthetic ECM without destroying cell-cell adhesions. This can be done by using a temperature-sensitive hydrogel which allows for spontaneous detaching when the temperature is decreased. "Sheets" of cells created in this manner can be stacked on top of each other (but only to a certain extent- if you stack too many sheets, the cells in the middle won't get enough nutrients).
Skeletal muscle
Skeletal muscle can be derived from satellite cells, bone marrow-derived stem cells, adipose-derived stem cells and embryonic stem cells. They are located under the basal lamina, which is located between the muscle cell and ECM, and are identified by the markers Pax3 and Pax7. When muscle fibres are damaged, they can differentiate into myoblasts, which can proliferate and migrate through the injury site. Myoblasts can then fuse and mature, regenerating the muscle fibre.
Integrin is not the only important protein involved in cell-ECM adhesions. Other important proteins are the dystroglycan complex, which binds to actin via dystrophin (which, as you may remember, is deficient in muscular dystrophy). Dystrobrevin may also be associated with the dystroglycan complex and dystrophin. Other important proteins involved in muscle fibre connections are N-cadherin and components of desmosomes (I swear I've written about these types of connections before, but can't find any posts. Oh well).
Since we're onto mechanobiology, we need to talk about mechanical forces that affect muscle differentiation and so forth. Striation of myotubes (which is due to the alignment of actin and myosin) depends on the underlying stiffness: stiffnesses of around 8-11kPa (usual muscle stiffness) result in the striation of muscle, whereas higher and lower stiffnesses do not. Mechanosensitive proteins are also involved in the maturation of satellite cells: in the beginning stages of maturation, YAP expression is increased and YAP translocates to the nucleus, but later on it is phosphorylated and translocates to the cytoplasm, where it is degraded.
Only one more lecture to go!
Skeletal muscle can be derived from satellite cells, bone marrow-derived stem cells, adipose-derived stem cells and embryonic stem cells. They are located under the basal lamina, which is located between the muscle cell and ECM, and are identified by the markers Pax3 and Pax7. When muscle fibres are damaged, they can differentiate into myoblasts, which can proliferate and migrate through the injury site. Myoblasts can then fuse and mature, regenerating the muscle fibre.
Integrin is not the only important protein involved in cell-ECM adhesions. Other important proteins are the dystroglycan complex, which binds to actin via dystrophin (which, as you may remember, is deficient in muscular dystrophy). Dystrobrevin may also be associated with the dystroglycan complex and dystrophin. Other important proteins involved in muscle fibre connections are N-cadherin and components of desmosomes (I swear I've written about these types of connections before, but can't find any posts. Oh well).
Since we're onto mechanobiology, we need to talk about mechanical forces that affect muscle differentiation and so forth. Striation of myotubes (which is due to the alignment of actin and myosin) depends on the underlying stiffness: stiffnesses of around 8-11kPa (usual muscle stiffness) result in the striation of muscle, whereas higher and lower stiffnesses do not. Mechanosensitive proteins are also involved in the maturation of satellite cells: in the beginning stages of maturation, YAP expression is increased and YAP translocates to the nucleus, but later on it is phosphorylated and translocates to the cytoplasm, where it is degraded.
Only one more lecture to go!
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