Stem cells age-discriminate organelles to maintain stemness

IMAGE: Human mammary stem-like cell apportions aged mitochondria asymmetrically between daughter cells. Mitochondria were labeled age-selectively red 51 hours prior to imaging, leaving mitochondria that are younger unlabelled. The daughter cell…
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Credit: Julia Döhla

Tissue stem cells, that continuously renew our tissues, can divide asymmetrically to produce two types of daughter cells. One will be the new stem cell, where as the other will give rise to the differentiating cells of the tissue.

A study jointly lead by laboratories in the Institute of Biotechnology and Massachusetts Institute of Technology (MIT) investigated whether stem cells may also use asymmetric cell division to reduce accumulation of cellular damage. Damage buildup can cause stem cell exhaustion that results in reduced tissue renewal and aging.

Researchers developed a novel approach to follow cellular components, such as organelles, age-selectively during cell division.

“We found that stem cells segregate their old mitochondria to the daughter cell that will differentiate, whereas the new stem cell will receive only young mitochondria” says Pekka Katajisto, a Group leader and Academy research fellow at BI.

Mitochondria appear to be particularly important for stem cells, as other analyzed organelles were not similarly age-discriminated, and since inhibition of normal mitochondrial quality control pathways stopped their age-selective segregation.

“There is a fitness advantage to renewing your mitochondria,” says David Sabatini, Professor at MIT and Whitehead Institute. “Stem cells know this and have figured out a way to discard their older components.”

While the mechanism used by stem cells to recognize the age of their mitochondria remains unknown, forced symmetric apportioning of aged mitochondria resulted in loss of stemness in all of the daughter cells. “This suggests that the age-selective apportioning of old and potentially damaged organelles may be a way to fight stem cell exhaustion and aging,” says Katajisto.

Katajisto laboratory is now exploring how old mitochondria differ from old, and whether this phenomenon occurs in other cell types beyond the human mammary stem-like cells examined here as well as in in vivo.


Pekka Katajisto, Julia Döhla, Christine Chaffer, Nalle Pentinmikko, Nemanja Marjanovic, Sharif Iqbal, Roberto Zoncu, Walter Chen, Robert A. Weinberg, David M. Sabatini. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science 2.4.2015