Researchers have found a previously unidentified mechanism that helps explain why stem cells undergo self-renewing divisions but their offspring do not.
"This finding stands to change the way we think about how stem cells and their neighbors communicate with one another,” said Michael Buszczak, PhD, Associate Professor in the Department of Molecular Biology and at the Hamon Center for Regenerative Science and Medicine at University of Texas Southwestern Medical Center in Dallas. He collaborated on this study with Yukiko Yamashita, PhD, Associate Professor of Cell and Developmental Biology at the University of Michigan Life Sciences Institute in Ann Arbor, Michigan.
Scientists have been working to understand how the signaling between niches—specialized environments that help to maintain stem cells in an undifferentiated and self-renewing state—and stem cells works.
What they knew already was that the niche produces signals and growth factors essential for stem cell maintenance. But what they didn’t know were the mechanisms communication from the niche to the stem cells, but not to their differentiating daughter cells.
“These signals act over a short range, so only stem cells—but not their differentiating progeny—receive the self-renewing signals,” said Dr. Buszczak. “What we discovered was that the stem cells form microtubule-based nanotubes, which extend into the niche. These threadlike nanotubes act like straws to tap into the niche and allow signaling to occur specifically in the stem cell.” The findings are published in the journal Nature.
First author Mayu Inaba, MD, PhD, a postdoctoral research fellow at the University of Michigan and a visiting senior fellow in Molecular Biology at UT Southwestern in the Buszczak lab, noticed thin projections linking individual stem cells back to a central hub in the stem cell niche.
Dr. Yamashita looked through her old image files and identified the same connections in numerous images.“I had seen them, but I wasn’t seeing them,” she said.
The findings are important groundwork for understanding how stem cells reproduce and how miscommunication between cells can result in diseases like cancer. Too much stem cell production, for example, can lead to cancerous growth. Too little reproduction can result in inadequate renewal of cells and underlies the aging process.
“We hope to use this information as a foundation for understanding how perturbations in normal gene expression programs cause disease,” Dr. Buszczak said.