New “Time Machine” Technique Unveiled to Measure Cells

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Dendritic Cell Production

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Dendritic cells (co-stained Red/green) in a lymphoid hair follicle (peyer’s spot) draining pipes the intestinal tract (blue). Credit: Wang Cao and Shengbo Zhang, WEHI

Using a brand-new single-cell strategy, WEHI scientists have actually discovered a method to comprehend the programs behind how stem cells make specific cell types.

The research study exposed 30 brand-new genes that program stem cells to make the dendritic cells that kick-start the immune reaction.

By discovering this procedure, the scientists hope they will have the ability to discover brand-new immunotherapy treatments for cancer, and strategy to broaden this strategy in other locations such as finding brand-new drug targets in growth initiation.

At a glimpse

  • WEHI scientists have actually established a brand-new single cell technique to comprehend the programs behind what triggers stem cells to make specific cell types.
  • By screening children of a single stem cell in various parallel tests, scientists discovered 500 genes that anticipated dendritic cell fate.
  • Using a CRISPR screen, they found 30 essential genes among the 500 that program dendritic cell production.
  • Researchers plan to broaden usage of this strategy to discover the ‘big bang’ minute in cancer advancement to determine brand-new drug targets to combat cancer.

Studying ‘sister’ cells

Led by Dr. Shalin Naik, Dr. Luyi Tian, Ms. Sara Tomei, and Mr. Jaring Schreuder and released in Immunity, the research study detailed the procedures associated with kick-starting the generation of dendritic cells driven by the hormonal agent Flt3 ligand, which is utilized in immunotherapy.

The research study group established a brand-new strategy to connect the gene expression of a single cell with what cell types it made.

“We invented a technique called ‘SIS-seq’ in order to study ‘sister’ cells that descended in parallel from the ‘mother’ stem cell,” Dr Naik stated.

“As RNA sequencing ruins the single stem cell, you are just able to determine the hereditary contents of the cell however lose the possibility to understand what it would have made. So, there is no chance of then returning in time to discover that out.”

“By letting a single stem cell divide only a few times, not all the way, we were able to test the sisters separately. Some were tested for what they made, and others were tested for their genetic contents.”

“In this way, we have been able to link the genes with the cell types that are made.”

Discovery of 30 brand-new genes

Dr. Naik stated the findings would not have actually been possible without advances in innovation that made it possible for the group to address numerous concerns concurrently. “Using a CRISPR screen, we tested 500 genes that predicted dendritic cell fate and discovered 30 new genes that actually program dendritic cells to be made,” he stated.

Dr. Naik stated the advancement might lead the way for brand-new drug targets to combat cancer and enhance immunotherapy treatment.

“We’ve now got a list of genes to try and generate or boost human dendritic cells in a petri dish for immunotherapy,” he stated. “And we are going to expand the use of this technology to find the genes that program the generation of each of the different human immune cell types.”

Finding the ‘big bang’ of cancer initiation

By taking a look at cells at the single-cell level utilizing this strategy, scientists likewise plan to discover the ‘big bang’ minute in cancer advancement in order to develop brand-new drug targets to combat cancer and enhance immunotherapy.

“Using our time machine technique, we hope to be able to pinpoint which of the normal programs in tissue generation are hijacked by cancer-causing genes in single cells and then use this information to find new targets for therapy,” Dr. Naik stated.

Reference: 15 April 2021, Immunity.
DOI: 10.1016/j.immuni.2021.03.012

This work was enabled with financing from the National Health and Medical Research Council, the Australia Research Council, the Victorian Cancer Agency and the Victorian Government.