KEEPING STEM CELLS FROM CHANGING FATES

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KEEPING STEM CELLS FROM CHANGING FATES

http://www.hopkinsmedicine.org/news/media/releases/keeping_stem_cells_from_chang\

ing_fates

Release Date: 09/08/2010

s Hopkins researchers have determined why certain stem cells are able to

stay stem cells.

The report in the June 4 issue of Cell Stem Cell reveals that an enzyme that

changes the way DNA is packaged in cells allows specific genes to be turned on

and off, thereby preventing a stem cell from becoming another cell type.

Each cell has to fit in 6 feet of highly organized and carefully packaged DNA.

Some regions of the DNA are more tightly compacted than others and this

structure is dynamic. There are specific enzymes that change how condensed the

DNA is to help turn genes on and off. The genes that are turned off generally

are found in tightly condensed DNA. To turn genes on, the DNA around those genes

is loosened so that activators and other proteins can interact with the DNA.

The s Hopkins researchers believed that restructuring the DNA by proteins

that make up chromosomes could play a role in deciding if a stem cell was going

to change into another cell or stay a stem cell, since change in the DNA

packaging would allow for many genes to be turned off and other genes to be

turned on.

By genetically engineering flies to lack several proteins involved in packaging

DNA, in the stem cells of the testes in fruit flies, the research team found

that if the enzyme NURF is removed from testis stem cells, the stem cells

disappeared. A constant supply of stem cells in the testes is responsible for

making cells that eventually become sperm. More staining of the testes with

colored markers showed that these cells hadn't gone away completely, but were

becoming another cell type, sperm cells.

" This experiment was really hard to do, " says Matunis, Ph.D., professor of

cell biology from the s Hopkins School of Medicine. " As soon as you remove

NURF from these cells, they leave, so you have to take a lot of samples to see

how the cells are moving, since we are not looking at living moving cells but

rather individual flashes in time. "

So how does NURF keep stem cells as stem cells? NURF can both turn on and turn

off genes. " We still don't know what is happening in this case with how NURF

regulates genes to keep stem cells from changing, " says Matunis.

Matunis' group last year discovered proteins that were able to prevent stem

cells from becoming other types of cells in the fruit fly testes. Now they

showed that these same proteins also work with NURF to keep stem cells from

changing. " By any means this isn't the only pathway though, it's just the one we

know more about " says Matunis. " It's probably a tangled hair ball of all kinds

of signals going on in these cells that prevent these stem cells from

differentiating. "

NURF keeps stem cells from changing in fruit fly testes, but whether NURF keeps

other stem cells from changing still needs to be tested. Matunis believes that

proteins similar to NURF will factor into whether a cell decides to change or

not in other cell types.

Graduate student Cherry is an author on the paper in addition to

Matunis.

Funding for the research was provided by grants from the NIH/NICHD.

On the web:

Matunis website: http://www.hopkinsmedicine.org/cellbio/dept/MatunisProfile.html

Cell Stem Cell: http://www.cell.com/cell-stem-cell/