Wnt signaling proteins act locally on embryonic stem cells

March 21, 2013 § Leave a comment

A dividing stem cell partitions and aligns its chromosomes according to the position of a bead coated with a Wnt protein. [Video courtesy of Shukry Habib, Roel Nusse, Bi-Chang Chen and Eric Betzig (HHMI, Janelia Farm Research Campus)]

It appears that Wnt proteins are like real-estate agents and think “location, location, location.” In a paper just out in Science, researchers report that these important developmental signaling molecules work locally on embryonic stem cells to guide them toward asymmetric division and differentiation.

Stem cells are pluripotent, meaning that they have the potential to become almost any kind of cell type in the body. They divide asymmetrically, not evenly down the middle. Asymmetric cell division also happens in cancer cells. Despite the importance of asymmetric cell division, not much is known at the single-cell level about its mechanics.

A signaling pathway involving Wnt proteins is known to be involved in asymmetric cell division. “We understand a great deal about Wnt signaling at the level of their transcription targets,” explains Roel Nusse, a Howard Hughes Medical Institute investigator at Stanford University who is the senior author on the paper. “But much less is known about how the Wnt signal leads to oriented cell divisions.”

Based on worm studies, there is evidence that Wnt proteins act locally, says Nusse. But no one had ever studied single stem cells using single Wnt proteins to see if they elicited particular directional responsesduring cell division.

So Nusse, first-author Shukry Habib, also at Stanford, and colleagues developed a method based on time-lapse microscopy and beads coated with various Wnt molecules. They exposed each bead to a single mouse embryonic stem cell to see how the Wnt molecule affected cell division.  

They demonstrated that Wnt3a, which maintains a stem cell’s pluripotency, caused daughter cells to have different fates. Daughter cells closest to the beads maintained their pluripotency, but daughter cells farthest from the beads began to differentiate.

Nusse says the next step is to study other cell types, including human stem cells, and tease out the molecular events that get triggered by a localized Wnt signal that ultimately leads to  asymmetric cell divisions.

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