Memorial Sloan Kettering Cancer Center (MSK) researchers have just taken a leap forward. In the process, they’ve vastly deepened our understanding of how primary cilia — slender, hair-like structures that extend from the surface of nearly every human cell — get built. Yinwen Liang and Alexandra Joyner, who both contributed to that study, were among the researchers who identified the two transcription factors—SP5 and SP8. These determinants act as an on-off switch to launch the assembly of primary cilia. This finding could lead to new breakthroughs in treating other diseases linked to these ciliopathies.
Primary cilia are some of the most important – yet least understood – structures found on nearly every cell in the human body. They serve as a vital mechanism for cellular signaling and communication. In other cell types, these important projections are missing. Liang first suspected that cells lacking primary cilia do so by actively promoting their disassembly. To gain a more detailed understanding, the research team turned to single-cell RNA sequencing (scRNAseq). This strategy revealed over 100 novel genes with higher expression in ciliated cells versus non-ciliated cells.
The Role of SP5 and SP8 in Cilium Formation
These key findings from our research made it abundantly clear that SP5 and SP8 serve critical functions to regulate the formation of primary cilia. Their findings showed that these transcription factors are very active in every cell type known to have primary cilia. They are still dormant in cell types that do not have this architecture. The results of the study indicated that SP8 overexpression was sufficient to induce the formation of primary cilia. This happens even in cells that normally do not generate them.
“If you add SP8 to extraembryonic cells, many of the cells now make cilia,” – Dr. Joyner.
This surprising finding underscores how important SP5 and SP8 could be to therapeutic strategies. These targets may be critical in developing therapies for disorders where primary cilia are defective. By manipulating these genes, researchers can investigate thrilling new approaches to restoring or improving cilium formation in affected cells. This historic advance opens new horizons for far-reaching new treatments and therapies.
Liang emphasized the significance of their findings, stating, “We see it as a big breakthrough to find the upstream transcription factors that switch the whole thing on.” This understanding of gene regulation is incredibly promising. In the long term it would produce cures for diseases known as ciliopathies, which are diseases caused by defects in ciliary structure or function.
Implications of Primary Cilia Research
Primary cilia are key players, not just in maintaining normal cellular function, but as integral parts of multiple diseases. Dysfunctional cilia underlie a striking and growing list of health problems. They have been implicated in diseases ranging from polycystic kidney disease, retinitis pigmentosa, to various genetic syndromes. As a result, knowing how cilia are built and controlled is key to becoming more effective with therapies.
The research team’s identification of more than 100 genes involved in cilia formation and function marks a significant step forward. In the context of primary cilia, researchers are just beginning to map the genetic landscape. With this insight we can better appreciate its wider impact on cell biology and disease pathology.
Liang’s upcoming endeavors promise an ongoing dedication to transcribing these fundamental findings into the clinical advances we seek. She will be leaving MSK to begin her own laboratory in China. Her research will tackle the problem of uncovering the fundamental mechanisms of cilia formation for translating into clinical interventions for patients affected by ciliopathies.
“My long-term goal is to improve our understanding of how cilia are formed and then use that information to benefit the clinical study of ciliopathies,” – Dr. Liang.
Collaborative Efforts and Future Directions
The artistic collaboration between Liang and Joyner has been extremely fruitful, with their combined experience bringing to life this groundbreaking discovery. Joyner’s lab provided valuable tools for studying gene regulation during developmental processes, enhancing the research’s depth and scope.
The researchers are excited to continue to explore the mechanisms by which SP5 and SP8 control cilium formation. They hope to study additional genes involved in this complex biological process. Their work underscores the importance of interdisciplinary collaboration, as combining different areas of expertise can yield significant advancements in understanding cellular functions.
The impact of this research goes far beyond the collegiate environment. Scientists like Dr. Garcia are relentlessly pursuing the primary cilia’s secrets. Importantly, this research lays the groundwork for developing innovative therapeutic strategies to combat ciliopathies and other related conditions. By applying understanding learned through foundational science, they can push themselves to deliver practical answers that make a difference in patients’ lives.