Embryology Biology 441 Spring 2013 Albert HarrisDifferentiation
Each human body is made of about 250 differentiated cell types.
For example:
Skeletal muscle cell. Two kinds of smooth muscle cell. Chondrocyte. Osteocyte. Retinal Ganglion cell. Rod cell (of sensory retina) Three kinds of Cone cells of retina. Liver cell. Endothelial cell
That's 13 examples. (Amoebae; Spores; Stalk Cells; another kind of stalk cell that supports the stalk base) "Regulation" in slime molds is mostly differentiation of correct percentages of amoebae into spore & stalk. Sponges & Hydra have about a dozen differentiated cell types. (each) Their shapes are caused by continual active cell rearrangements (independent of original location)
"Housekeeping genes": DNA that is transcribed in all or nearly all differentiated cell types
"Luxury genes": Genes that are only transcribed in certain differentiated cell types Stem cells: Some examples: Hemopoietic cells in our bone marrow that remain undifferentiated, continue to divide, with some of them differentiating into red blood cells, others differentiating into different kinds of white blood cells (maybe a dozen differentiated cell types)
Bone marrow transplants are injections of hemopoietic cells from another person, or sometimes from oneself. The deepest layers of the epidermis consist of another kind of stem cells that divide and differentiate into new skin cells. Our intestinal lining is constantly replaced by another kind of stem cells, located at the bottom of invaginations (which are poetically called "crypts") In recent years, lots of people began to refer to cells of the inner cell mass as being "embryonic stem cells" This is a good example of propaganda, by means of expanding the definition of a biological term, implying "facts" that are not yet actually known to be true. This changed usage gives an idea to the public that procedures like bone marrow transplants and skin grafts can be necessarily be developed for replacing the spinal cord, bones, muscles, eyes, anything, combined with a second idea that the best source for cells to rebuild organs is left-over human blastocysts . An average of about six such left-over blastocysts are produced for every in vitro fertilization (many or most of which would have terrible birth defects if they developed into actual babies). Future MDs should give serious thought to these and other moral issues related to human embryos. Don't leave it to newspaper editors and religious leaders, with no knowledge or interest in facts.
My own opinion is that more effort should be given to discovering how to convert differentiated cells back to an undifferentiated state, and also to normal mechanisms by which organs are formed. Less than a hundredth as much grant money has been given to these questions as to cells from embryos. The political-religious fight has covered up the lack of knowledge of how to use those cells, even in mice. Both sides have been too busy fighting to pay attention to embryological facts, or to learn more. Changing the meaning of medical terminology has "the power to cloud men's minds." (women, less so)
Sometimes you can convince people of something just by choice of vocabulary. If people start calling kangaroos "Australian horses" then people will think they can put saddles on them and ride them around, and if people argue that it's cruel to the kangaroos and shouldn't be done, then they will be absolutely sure that it's possible. The argument about the cruelty will completely smother the argument about whether it's possible to do it in the first place. ------------------------------------------------------------------------------------------------------ Some facts about cytodifferentiation, that nobody knows the explanations for: Differentiation is << mutually exclusive >> (for lack of a better term)
For unknown reasons, no cell can differentiate into two or more different cell types at the same time. If you fuse a liver cell with a heart cell, the resulting cell line stops making luxury proteins for both heart cells and for liver cells. Three interesting exceptions:
1) Bird red blood cells do have nuclei, but these are very inactive and shrunken in size.
(Mammal red blood cells eject their nucleus during differentiation, to make space for hemoglobin) 2) Skeletal muscle cells have hundreds of nuclei. Fusing one or few human liver cells into a bird skeletal muscle cell causes the liver cells to stop making liver luxury proteins AND ALSO to start transcribing human muscle-specific luxury genes.
3) Cancer cells sometimes transcribe combinations of luxury genes for more than one cell type.
For example, the first symptoms of cancers of lung cells can be over-production of some hormone that normally is made only by some specific endocrine gland. Brain cancers usually consist of one or the other of two differentiated cell types. In advanced stages of these cancers, it becomes difficult or impossible to distinguish which of the two cell types they are made of. A fourth interesting fact is that fusing cancerous cells from two different lines usually produces cells that are non-cancerous in their growth and behavior. This was not at all what was expected; so they tried many times! Maybe turning off luxury genes can also turn off oncogenes? Nobody knows. -------------------------------------------------------------------------------------------------------------------------- SOME OTHER INTERESTING (important) FACTS: The amount of each protein made in differentiated cells (usually?) is exactly proportional to the number of copies of the gene that codes for it. (There may be exceptions; but in many studies the amounts were linearly proportional to gene number - which was NOT expected. Most researchers expected feedback control. That would even out gene activity. One extra copy of a chromosome results in half again (150%) of the normal amount of each protein coded for by the genes on that chromosome. True in flies; true in people. The size (volume) of each cell in an animal is exactly proportional to the ploidy. Tetraploid animals have exactly double-sized cells. But the size of the animal is NOT changed; neither are the sizes of organs different. Therefore, tetraploid animals have half the number of cells. (And so do all the organs). Haploid animals have twice as many, half-sized cells. Many species of frogs are tetraploid versions of other species. Haploid, triploid, and tetraploid mammals die late during embryonic development. (Fankhauser did much research on this) I can't quite believe that double-sized red blood cells could fit through normal diameter capillaries, so maybe there are some exceptions. -------------------------------------------------------------------------------------------------------------------------- What molecular mechanism "turns on" the correct combinations of luxury genes? Does each of the 250 cell types have its own special promoter sequence? (or set of sequences) That is what most scientists expect; and what has been proven true in many cases; but not all. If you go into research, & "genomics" & proteomics this is a key set of questions. Facts haven't fallen into place as expected. That suggests to me that some big idea has been missed. One unexpected discovery is that differences in the flexibility of substrata can control differentiation! (I regret very much missing this discovery) In the specific case of chondrocyte differentiation, I was among those who tried to prove that tighter packing among limb bud cells is what controls where cartilages will form. Actually, this has not yet been proven.
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