Stem Cells Determine Their Daughters' Fate

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Stem Cells Determine Their Daughters' Fate

http://www.medicalnewstoday.com/medicalnews.php?newsid=63233

From roundworm to human, most cells in an animal's body ultimately

come from stem cells. When one of these versatile, unspecialized

cells divides, the resulting " daughter " cell receives instructions

to differentiate into a specific cell type. In some cases this

signal comes from other cells. But now, for the first time,

researchers at the Carnegie Institution's Department of Embryology

have found a type of stem cell that directly determines the fate of

its daughters.

The finding, reported in the online edition of the journal Science,

could transform our basic understanding of stem cells by

demonstrating that some tissues maintain themselves throughout life.

It could also prove valuable in the fight against some cancers.

" We found that stem cells can participate actively in determining

what type of cell their daughters will become right at the moment of

stem cell division, " said Embryology director and study co-author

Allan Spradling. " This suggests that tissue stem cells might not

just be a source of new cells, but could actually be the 'brains' of

the tissue - the cells that figure out what type of new cell is

needed at any given moment. "

Because they truly can become any cell in the body, " embryonic " stem

cells tend to receive a lot of attention. Yet " adult " stem cells

remain in fully-developed organisms, where they replace specific

cell types lost to age or disease. Spradling and postdoctoral

researcher Ohlstein performed the study using intestinal

stem cells (ISCs), a type of adult stem cell in the fruit fly

Drosophila melanogaster that they discovered only a year ago.

These cells directly use the " Notch " signaling pathway, a system

well-known to biologists, to replenish one of two cell types in the

fruit fly's gut. The fate of any given daughter appears to depend on

a protein, called Delta, which sits on the surface of the ISC and

activates the Notch pathway in its daughters.

" Delta and the Notch receptor protein are both attached to the

surface of cells, and don't float around freely, so we always have

to assume that the Delta signal comes from nearby cells, " Ohlstein

said. " But the ISC is literally about as nearby as you can get. "

Most daughters receive a strong Delta signal from the ISC and become

enterocytes (ECs) - cells that line the inside of the gut and absorb

nutrients. But when the Delta signal is weak, the daughters will

become hormone-generating enteroendocrine cells. For every 15-20 ECs

it creates, a given ISC will also produce two enteroendocrine cells,

usually in matched pairs at the same time.

Spradling and Ohlstein tracked the whereabouts of Delta, Notch, and

several other related proteins using fluorescent marker molecules.

They found that most ISCs have large amounts of Delta protein. This

made it relatively easy to single out ISCs during the experiments -

usually a significant challenge with stem cells - and to track where

Delta molecules moved over time.

Delta seems to control not just what types of new cells are made,

but also puts the brakes on excessive cell division. In several

experiments where Delta or other Notch signaling genes were disabled

or blocked, the daughter cells continued to divide, eventually

producing tumors.

" Each individual stem cell seems to have a great degree of

independence from the rest of the animal's body, " Spradling

explained. " On one hand, the ISCs can respond quickly to the needs

of the gut lining as it loses cells. On the other hand, they seem

rather vulnerable to losing control of cell division. "

It remains to be proven whether ISCs require a specific

microenvironment created by neighboring cells, known as a niche, as

other types of stem cells in Drosophila and mammals do.

Understanding such a niche could have huge implications for the

study of certain kinds of cancer, including those of the brain and

intestine.

Future studies of ISCs might also reveal how the mammalian intestine

responds to nutrition, stress, and illness. Like the fruit fly gut,

mammalian intestines also contain large numbers of dispersed stem

cells.

" Our hope is that the distinctive molecular properties of Drosophila

ISCs we discovered will now allow mammalian intestinal stem cells to

be definitively identified and better studied, " Spradling added.

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The Carnegie Institution of Washington

(http://www.carnegieinstitution.org/), a private nonprofit

organization, has been a pioneering force in basic scientific

research since 1902. It has six research departments: the

Geophysical Laboratory and the Department of Terrestrial Magnetism,

both located in Washington, D.C.; The Observatories, in Pasadena,

California, and Chile; the Department of Plant Biology and the

Department of Global Ecology, in Stanford, California; and the

Department of Embryology, in Baltimore, land.