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In most mammals, females have two X chromosomes and males have one X and one Y chromoso.
Human embryonic stem cells (hESCs) hold great promise for early developmental studies as well as for regenerative medicine for diseases ranging from type 1 diabetes to Parkinson.
"If you can't fully maintain hESCs in culture, then you can't use them for any downstream applications," said Sundeep Kalatm, .
Their main suspicion was the substance used to grow the cells, called the culture medi.
"We investigated the difference in the composition of the two media and determined that lithium chloride is present in mTeSR1 but not in Xenofree," Kalatm sa.
Lithium chloride is sometimes added to the culture medium to promote stem cell proliferation, however, it is known to interfere with many cell signaling pathways by inhibiting the GSK-3 prote.
Confirming that lithium chloride was the culprit, they added this compound to Xenofree medium and found a loss of X-inactivati.
"In terms of our understanding of X-chromosome inactivation, our study provides a possible new model for the regulation of this process," their study showed when the researchers used GSK-3 inhibitors like lithium Need to be more cautio.
The role of ancient X-linked genes in the induction of X inactivation
Another paper by Kalantry and colleagues in Nature Communications provides insight into the evolution of mammalian X-inactivati.
In female cells, deletion of Kdm5c on both X chromosomes almost completely turned off X-inactivati.
Kdm5c is an ancestral X-linked gene shared by all mammalian speci.
"If a female cell expresses a higher-than-normal level of an X-linked gene, the cell typically becomes damaged and dies," Kalantry sa.
The team hoped next to explain the stochastic process that determines which X is silenced in female cells: the mother's X-silence or the father.
“Preventing erosion of X-chromosome inactivation in human embryonic stem cel.
“Activation of Xist by an evolutionarily conserved function of KDM5C demethylase” Nature Communications 13, 2602 (202