Long read sequencing and cell/organoid differentiation

DigiTwins partner Prof. George Church from Harvard Medical School and his group are taking multiple approaches towards the medicine of the future with advances in long-read sequencing and cell/organoid differentiation for autologous transplantation. 

The induced-pluripotent stem cell (iPSC) technology has opened new frontiers to regeneration and organ replacement. Many protocols have been generated and optimized to derive different human cell types for developmental and therapeutic purposes. In our lab, we are interested in generating any cell type found in the body faster and more efficiently than ever before using combinations of transcription factors (TF) found in our complete human TFome library. With all the human TFs at our disposal, we have shown fast differentiation of neurons and oligodendrocytes that can be used to treat neurological and neurodegenerative diseases like Alzheimer’s and Multiple Sclerosis among others.  We are also working to vascularize the organoids we are growing from differentiating iPSCs, in order to enable nutrients and oxygen to penetrate deep inside these tissues. This will promote growth and development of complex organs and tissues that mimic what we see in vivo. 

One additional promising example comes from our collaboration with another Harvard lab whereby iPSCs were induced to differentiate into kidney podocyte cells in defined cellular media. These cells were then used to engineer a Glomerulus-on-a-chip microfluidic device that can be used to test biological functions of normal vs diseased kidney cells, and also enable drug screening in human rather than non-human animal models. 

In another recent publication from our lab, we expand the uses of the CRISPR/Cas9 toolbox to tracing and recording genetic information from differentiating cells and developing tissues and assessing the final accumulation changes over time by sequencing. We can use this technology to track the cells we transplant and understand how well they graft in different individuals, and at what efficiencies they contribute to the desired cell population, as we collect more personalized medical information for future patients. 

Our group is also working very hard to establish alternative DNA sequencing platforms that accelerate easy, fast, low-cost, and efficient sequencing of complex mammalian genomes. Among them, nanopore sequencing, where a electric current applied to small molecular pores differentiates each base of the DNA as it is being synthesized by the polymerase, has tremendous potential to synthesize longer DNA fragments that can be read in real-time in more portable sequencing devices. Sequencing whole genomes cheaply is at the crux of personalized medicine and our efforts are moving us closer to the <$1000 genome in the very near future. 

Article Source: https://www.digitwins.org/blogpost-blog-2-long-read-sequencing-and-cell-organoid-differentiation

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No GA727816.

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