For many commuters, good maintenance may make the difference between getting to work on time or waiting in the cold to be rescued from the roadside at 8:00 in the morning. Like any vehicle, a cell is a well-oiled machine with many parts that are continuously replaced or repaired to ensure durability. Now, new research from the Whitehead Institute shows that how new and old parts are allocated when cells divide is important for the longevity of stem cells.
One neat property of stem cells is that they divide asymmetrically to produce a copy of themselves, and another cell committed to differentiate. Exactly how this happens in mammalian stem cells is still unclear, but stem cells should be no exception to the rules of construction: the quality of workmanship depends on that of the starting materials.
At least this is how David Sabatini and his international team of biochemical engineers reason in their new study published in Science: organelles sustain damage during the lifetime of a cell, so ‘old’ damaged organelles should be inherited by the committed cells of asymmetric division, to avoid depleting the stem cell pool.
To monitor the fate of organelles in cultures of human mammary stem cells, the team labeled proteins specific of various cell organelles with a photoactivatable green fluorescent protein (paGFP) that lights up temporarily after exposure to UV light. The tagged proteins continue to be synthesized after the pulse of UV creating ‘old’ (fluorescing) and ‘young’ (non-fluorescing) organelles.
- In differentiated cells, ‘old’ organelles were equally distributed between daughter cells during cell division, whereas dividing stem cells gave six times more ‘old’ mitochrondria to one daughter cell than the other.
- Some clever engineering with SNAP-tag technology to create two fluorescently-labeled populations of mitochondria (one old and one new) confirmed these findings.
- Cells that received few ‘old’ mitochondria resembled the parental population and formed three times more mammospheres (a test of stemness) than cells that received many ‘old’ mitochondria.
- Down-regulation of proteins important for mitochondrial renewal prevented ‘old’ mitochrondria from being asymmetrically allocated, leading to a loss of stemness.
So when it comes to mitochondria, dividing stem cells apply a strict policy of out with the old and in with the new to ensure effective maintenance of their stem-like progeny.
Check out Science, April 2015 for your stem cell repair and maintenance manual.