TOP UNANSWERED QUESTIONS TO EXPLORE ABOUT STEM CELLS

Scientists have been studying adult stem cells for more than 40 years and embryonic stem cells for more than 20 years. They’ve uncovered a lot about both kinds of stem cells, but there’s a lot they still don’t know.


Questions researchers are still seeking answers to include the following:

✓ How many kinds of adult stem cells are there?

✓ Where do adult stem cells live in specific tissues?

✓ What control mechanisms do stem cells use to maintain their selfrenewal capabilities?

✓ What genetic mechanisms control stem cells’ ability to make one or more kinds of differentiated cells?

✓ Why don’t adult stem cells differentiate automatically when they’re surrounded by differentiated cells?

✓ Why can embryonic stem cells grow and make more of themselves in the lab for a year or more, while most adult stem cells have far more limited self-renewing capabilities in a Petri dish?

✓ How do stem cells know when to make more of themselves and when to make cells for specific tissues?

✓ Why don’t all stem cells “home in” to their proper location the way blood-forming stem cells do when they’re transplanted into a living body

✓ If you introduce stem cells into specific tissues in a living body, do they stay where you put them, or do they wander aimlessly around the body’s tissues?

✓ How long do transplanted stem cells stay in the body?

✓ If you reprogram adult cells to behave like embryonic stem cells, are the reprogrammed cells completely normal, or does the reprogramming process mess with the genetic instructions?

✓ In their normal environments (known as niches), can adult stem cells really make differentiated cells for tissues other than their tissue of origin?

✓ Is there a master adult stem cell — one that, like embryonic stem cells, can make any type of cell in the body?

Modern stem cell science is pretty young, so it’s not surprising that researchers still don’t know the answers to some relatively basic questions. As Lao Tzu, the father of Taoism, is credited with saying, “The wise man knows he doesn’t know.”

DNA STRUCTURE AND REPLICATION BASIC INFORMATION

DNA molecules are large, with RMMs up to one trillion (1012). Experimental work by Chargaff and other workers led Crick and Watson to propose that the three dimensional structure of DNA consisted of two single molecule polymer chains held together in the form of a double helix by hydrogen bonding between the same pairs of bases, namely the adenine–thymine and cytosine–guanine base pairs.

These pairs of bases, which are referred to as complementary base pairs, form the internal structure of the helix. They are hydrogen bonded in such a manner that their flat structures lie parallel to one another across the inside of the helix. The two polymer chains forming the helix are aligned in opposite directions.

In other words, at the ends of the structure one chain has a free 3’-OH group whilst the other chain has a free 5’-OH group. X-Ray diffraction studies have since confirmed this as the basic three dimensional shape of the polymer chains of the B-DNA, the natural form of DNA.

This form of DNA has about 10 bases per turn of the helix. Its outer surface has two grooves, known as the minor and major grooves respectively, which act as the binding sites for many ligands. Electron microscopy has shown that the double helical chain of DNA is folded, twisted and coiled into quite compact shapes.

A number of DNA structures are cyclic, and these compounds are also coiled and twisted into specific shapes. These shapes are referred to as supercoils, supertwists and superhelices as appropriate.

DNA molecules are able to reproduce an exact replica of themselves. The process is known as replication and occurs when cell division is imminent. It is believed to start with the unwinding of the double helix starting at either the end or more usually in a central section, the separated strands acting as templates for the formation of a new daughter strand.

New individual nucleotides bind to these separated strands by hydrogen bonding to the complementary parent nucleotides. As the nucleotides hydrogen bond to the parent strand they are linked to the adjacent nucleotide, which is already hydrogen bonded to the parent strand, by the action of enzymes known as DNA polymerases.

As the daughter strands grow the DNA helix continues to unwind. However, both daughter strands are formed at the same time in the 5’ to 3’ direction. This means that the growth of the daughter strand that starts at the 3’ end of the parent strand can continue smoothly as the DNA helix continues to unwind. This strand is known as the leading strand.

However, this smooth growth is not possible for the daughter strand that started from the 5’ of the parent strand. This strand, known as the lagging strand, is formed in a series of sections, each of which is still grows in the 5’ to 3’ direction.

These sections, which are known as Okazaki fragments after their discoverer, are joined together by the enzyme DNA ligase to form the second daughter strand. Replication, which starts at the end of a DNA helix,continues until the entire structure has been duplicated.

The same result is obtained when replication starts at the centre of a DNA helix. In this case unwinding continues in both directions until the complete molecule is duplicated. This latter situation is\more common.