Self-renewal and specialization are two opposing functions in progenitor cells. Scientists resolve the mechanisms behind the opposing developmental actions of beta-catenin, a co-activator of the established molecular Wnt signaling pathway, that paradoxically regulates both self-renewal and specialization of mammalian progenitor cells destined to become kidney cells.
The new study led by Andrew McMohan, PhD, chair of the department of stem cell biology and regenerative medicine at the Keck School of Medicine of University of Southern California, reports high levels of beta-catenin trigger a switch in part of the Wnt pathway that relies on transcription factors known as TCF/LEF.
In response to high levels of beta-catenin, the activating members of TCF/LEF switch places with the inhibiting members, effectively taking charge. This switch triggers progenitor cells to specialize into different types of kidney cells.
These findings are reported in the article “A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells” published in the journal eLife.
“Understanding how Wnt regulates these two very distinct cell outcomes of self-renewal and differentiation, which is very important for kidney development, is also important for understanding the development of other organs and adult stem cells, as Wnt signaling plays important roles in almost all developmental systems,” says Helena Bugacov, a current PhD student in the McMahon Lab and a co-author of the eLife study. “There is also a lot of attention from cancer researchers, as this process can go awry in cancer. Many therapeutics are trying to target this process.”
These findings provide insights on developing human kidney organoid cultures, which are important tools in basic and preclinical research that address problems in regeneration and development.