Some groups of these white blood cells, now called neutrophils, have a very different structure in their nuclei than most nuclei. Most cells have a rigid round or oval nucleus, but neutrophils differ in that their nucleus employs multiple leaflet structures, similar to those arranged in petals.
These unique nuclear shapes allow neutrophils to spread throughout the body to recognize and fight invading pathogens. While little is now known about the role of neutrophils in fighting infection, how this peculiar nuclear structure assembled has been a mystery since the 1880s.
Professors Indumathi Patta and Cornelis Murre, postdoctoral fellows in the UC San Diego School of Biological Sciences, collaborated with Dr. Ming Hu of the Cleveland Clinic to decipher the deformation puzzle of neutrophil nuclei.
We now know how these nuclear shapes are assembled, and it's a beautiful process," said Murre, a distinguished professor in the Department of Molecular Biology.
Indumathi Patta, a postdoctoral scholar at the University of California, School of Biological Sciences. **University of California, San Diego.
Researchers have combined an age-old staining procedure with an advanced technique called chromosome-conformation-capture studies to reveal how flower-like nuclei are assembled. While the chromosomes of round cells fold into stacked bundles of DNA rings, the neutrophil genome lacks such loops.
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Notably, when the researchers removed the chromatin loops, progenitor cells quickly transformed the circular nuclear shape into a petal arrangement, similar to the one found in neutrophils. This simple switch is also enough to activate thousands of genes associated with the inflammatory gene program, enabling neutrophils to fight invading bacteria.
After lifting the veil on the problem of neutrophil ring assembly, researchers now believe they have instructions to guide the development of new nuclear shapes.
Postdoctoral scholars at the University of California, School of Biological Sciences, Professor Indumathi Patta and Professor Cornelis Murre. **University of California, San Diego.
This could open an exciting new chapter for immunity, as it should theoretically be possible to alter the nuclear structure of killer immune cells so that they can more easily invade complex solid environments, such as tumors," Murre said. "Essentially, this could lead to the design of new nuclear shapes in effector immune cells, which is a new concept in development.
References: "Nuclear morphology is shaped by ring extrusion procedures" by Indumathi Patta, Maryam Zand, Lindsay Lee, Shreya Mishra, Alexandra Bortnick, Hanbin Lu, Arpita Prusty, Sara Mcardle, Zbigniew Mikulski, Huan-You Wang, christine s. cheng、kathleen m.Fisch, Ming Hu, and Cornelis Murre, February 14, 2024, Nature.
doi: 10.1038/s41586-024-07086-9
The authors of the study include: Indumathi Patta, Maryam Zand, Lindsay Lee, Shreya Mishra, Alexandra Bortnick, Hanbin Lu, Arpita Prusty, Sara Mcardle, Zbigniew Mikulski, Huan-You Wang, Christine Cheng, Kathleen Fisch, Ming Hu and Cornelis Murre.
Compiled from: scitechdaily