I read a cell-biology book by Cooper which mentions that there are three different types of differentiated cells: 1) those which are terminally differentiated and do not have any precursor left for their repair of any injury which may happen inthe future, such as heart cells, 2) the second type of differentiated cells are those which are kept in the G0 phase and as and when they are required they are used for replenishing the dead cells such as skin fibroblasts, smooth muscle cells, the endothelial cells that line blood vessels, and the epithelial cells of most internal organs, such as the liver, pancreas, kidney, lung, prostate, and breast and 3) the third type of cells are those differentiated cells which include blood cells, epithelial cells of the skin, and the epithelial cells lining the digestive tract which have short life spans and must be replaced by continual cell proliferation in adult animals. In the third type of cells, the fully differentiated cells do not themselves proliferate. Instead, they are replaced via the proliferation of cells that are less differentiated, called stem cells. Stem cells divide to produce daughter cells that can either differentiate or remain as stem cells, thereby serving as a source for the production of differentiated cells throughout life.
So, my doubt is, how these cells are maintained in cell-culture laboratories if the end terminal differentiated cells can not divide?
terminally differentiated cells (TD) cannot be propagated in culture. They do not divide. Usually the way to get them in vitro is by propagating proliferating precursors, which could be then switched to differentiation conditions (i.e. media, supplements or coating)
The answer to your question is complex and highly dependent on the cell type. Basically, anything that grows in cell-culture isn't completely terminally differentiated.
Many truly terminally differentiated cells, such as neutrophils, can be cultured, but do not grow.
Certain types of normal cells placed into culture are capable of a limited number of divisions before they undergo senescence after being cultured - that is highly cell type dependent. These lines are maintained by keeping frozen stocks that can be used to restart the culture.
Such cells are prone to undergo changes that will immortalize them, such as turning on telomerase, oncogene activations or tumor suppressor loss, because that is being selected for by the process of cell-culture.
Hi Puja,
what you wrote is completely true for cells inside tissues in living organisms. However, whenever a primary culture of terminally differentiated cells is established (for instance, fibroblasts from subcutaneous biopses), cells show some doubling capacity before reaching senescence, even if it is restricted to a limited number of passages (usually below 20). According to my experience, this capacity is directly proportional to the age of the donor but it is useful if you really need to perform your studies on primary cells. On the other side, if you need to maintain differentiated somatic cells in culture for an unlimited time, you should immortalize these cells with one of the several well established protocols. I'm not an expert in this specific field but I know that usually cell biologists induce immortalization with viral antigens like SV-40 T antigen, or via the inactivation of endogenous tumor suppressor genes, or also with the expression of Telomerase Reverse Transcriptase gene. After immortalization, cells show a sort of "tumoral-like" behaviour that allow them to indefinitely divide without experiencing senescence.
I hope that this answer clarified a little bit your doubts, anyway I think you could find many more pieces of information on PubMed!
Good luck
Tania Incitti
It all depends on your definition of terminally differentiated. As Michael suggests this term is now a little contentious.
Some cells such as chondrocytes have been considered to be terminally differentiated by some but if you do an ex-vivo culture they will divide to some extent. It is important to note that the cell culture environment is very different to that of the natural environment and has a huge effect upon cell behaviour. In my example chondrocytes completely change their behaviour when cultured and are said to dedifferentiate which should be impossible is they were terminally differentiated.
Terminal differentiation is controlled by very old molecular mechanisms of asymmetric division started in prokaryots (sporulation) and developed upon LUCA (last universal common ancestor) and ancient single-celld organisms (ASCO) to the eukaryotes today. Stem cells divide asymmetrically to produce daughter cells that can either differentiate or remain as self-renewing stem cells.
According to my experience with different ancient stem cells lines (AnSC) there are two different types of differentiated cells: 1) those which are reversible differentiated to mitotically repressed quiescent cells (QD cells) arrested in G0 and when they are passaged they are used for replenishing the mother stem cell line and 2) those which are irreversible differentiatiated, as precursors for TD cells. TD cells and their precursors cannot be propagated in culture and do not divide. QD cells re-enter cell cycle when passaged in appropriate hypoxic conditions. They progress cell cycle as new self-renewing stem cells (SR cells) giving rise by asymmetric divisions to new differentiated QD cells.
Ancient stem cell lines that I studied are unipotent but TD cells end as re-programmed cell system progenitor starting by appropriate environment a new life cycle (see my RG publications)
Thanks all of you for putting so much effort to answer my question! Your answers helped in coming to a conclusion that this topic is a little controversial and we can not go for only one concept rather we have to be flexible in thinking that according to the type of cells the scenario may change.
Thanks again!
