In order for the body's tissues to develop properly and maintain
themselves, renewal and differentiation must be carefully balanced.
When most cells divide, they simply make more of themselves. But stem
cells, which are responsible for repairing or making new tissue, have a
choice: They can generate more stem cells or differentiate into skin
cells, liver cells, or virtually any of the body's specialized cell
‘When stem cells divide, they can generate more stem cells or differentiate into any of the body's specialized cell types. Scientists have discovered that this pivotal decision can hinge on whether or not organelles are divvied up properly within the dividing stem cell.’
As reported in Science
, scientists at The Rockefeller University
have discovered that this pivotal decision can hinge on whether or not
tiny organ-like structures, organelles, are divvied up properly within
the dividing stem cell.
Senior author Elaine Fuchs, the Rebecca C. Lancefield Professor and head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, said,
"Our experiments suggest an unexpected role for the positioning and
inheritance of cellular organelles, in this case enzyme-filled
peroxisomes, in controlling this intricate balance."
An uneven division
The outer section of the skin, the epidermis, provides a protective
barrier for the body, and stem cells reside deep within it. During
development, these cells divide so that one renewing stem cell daughter
remains inward while the other daughter differentiates and moves outward
to become part of the epidermis' outer layers. First author Amma Asare,
a graduate student in the lab, wanted to know how skin cells first
emerge and begin this transition.
Looking in developing mouse skin, Asare devised an approach to
identify genes that help guide the balance between new cells that either
stay stem-like or differentiate. One particular protein, Pex11b, caught
her attention. It is associated with the membrane that surrounds the
peroxisome, an organelle that helps to free energy from food.
Asare showed that the protein seems to work by making sure the
organelles are in the right locations so they can be divided between the
daughter cells. In cells that lacked Pex11b, peroxisomes weren't
divvied up evenly - in some cases, one daughter cell ended up with all of
the peroxisomes and the other didn't get any at all. And for those
cells whose peroxisome distribution was disrupted, cell division took
longer, and the mitotic spindle, the structure that separates the
daughters' genetic material, didn't align correctly.
The net result of depleting skin stem cells of Pex11b, Asare found,
was that fewer daughter cells were able to differentiate into mature
A delay changes fate
The researchers next moved peroxisomes around in the cell using a
sophisticated laboratory technique, and the effect was the same. "If the
peroxisomes are in the wrong positions during cell division, no matter
how they get there, that slows down the process," Asare says.
The effect for the whole organism was dramatic: If peroxisome
positioning was disrupted in the stem cells, the mice embryos could no
longer form normal skin.
"While some evidence already suggested the distribution of
organelles, including energy-producing mitochondria, can influence the
outcome of cell division, we have shown for the first time that this
phenomenon is essential to the proper behavior of stem cells and
formation of the tissue," says Fuchs, who is also a Howard Hughes
Medical Institute Investigator.