Researchers from the School of Veterinary Medicine and Perelman School of Medicine have found that YY1 knockout pro-B cells can generate T lineage cells helping B cells produce antibodies.
Development of B cells, white blood cells that make antibodies, follows a progression of stages: common lymphoid progenitors, pre-pro-B cells, pro-B cells, pre-B cells, immature B cells, and then more mature and specialized B cells. By the time the development hits the pro-B stage, the cell is fated to stay a B cell rather than another type of cell.
He envisions the ability to temporarily knock down YY1, push cells in another direction, and then remove the block so now there is a new lineage. Muscle cells, for example, could be reimplanted into a patient with a muscle disease. Atchison says the basis for this paper began nearly a decade ago, with a former postdoctoral researcher who, looking at RNA sequencing data, had the idea that YY1 knockout pro-B cells could turn into T cells. Sarmistha Banerjee, first author on the paper, took over this work as a senior research investigator at Penn.
The sequencing data showed that as YY1 knockout pro-B cells developed in culture, 85% identified as monocytic or dendritic cells, which are involved in the presentation of antigens to B and T cells to mount an immune response, while only 3% identified as T cells. But incubation for three weeks resulted in the downregulation of most of these alternative lineage genes and increased expression of T lineage genes.
Looking forward, the mountain of data the team amassed"can be mined for a long time to look at what's happening when you knock out YY1," Atchison says."We've looked at a small handful of genes, but there's 20,000 genes in the genome, and there's a lot we can do just with the data we have." This work was supported by the National Institutes of Health and an Aspire award from the Mark Foundation for Cancer Research.Sarmistha Banerjee, Sulagna Sanyal, Suchita Hodawadekar, Sarah Naiyer, Nasreen Bano, Anupam Banerjee, Joshua Rhoades, Dawei Dong, David Allman, Michael L. Atchison.Scientists have developed an efficient, non-invasive, and pain-free method to generate canine-induced pluripotent stem cells . They identified six reprogramming genes that can boost canine ...
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