Nano-dissection identifies genes involved in kidney disease

October 4, 2013 by Catherine Zandonella
This is a scanning electron microscope micrograph of normal podocytes, which are cells responsible for the filtration functions of the kidney. Credit: Matthias Kretzler

Understanding how genes act in specific tissues is critical to our ability to combat many human diseases, from heart disease to kidney failure to cancer. Yet isolating individual cell types for study is impossible for most human tissues.

A new method developed by researchers at Princeton University and the University of Michigan called "in silico nano-dissection" uses computers rather than scalpels to separate and identify genes from specific , enabling the systematic study of genes involved in diseases.

The team used the new method to successfully identify genes expressed in cells known as podocytes—the "work-horses" of the —that malfunction in kidney disease. The investigators showed that certain patterns of activity of these genes were correlated with the severity of kidney impairment in patients, and that the computer-based approach was significantly more accurate than existing experimental methods in mice at identifying cell-lineage-specific genes. The study was published in the journal Genome Research.

Using this technique, researchers can now examine the genes from a section of whole tissue, such as a biopsied section of the kidney, for specific signatures associated with certain cell types. By evaluating patterns of gene expression under different conditions in these cells, a computer can use machine-learning techniques to deduce which types of cells are present. The system can then identify which genes are expressed in the cell type in which they are interested. This information is critical both in defining novel disease biomarkers and in selecting potential new drug targets.

By applying the new method to kidney biopsy samples, the researchers identified at least 136 genes as expressed specifically in podocytes. Two of these were experimentally shown to be able to cause . The authors also demonstrated that in silico nano-dissection can be used for other than those found in the kidney, suggesting that the method is useful for the study of a range of diseases.

The computational method was significantly more accurate than another commonly used technique that involves isolating specific cell types in mice. The nano-dissection method's accuracy was 65% versus 23% for the mouse method, as evaluated by a time-consuming process known as immunohistochemistry which involves staining each gene of interest to study its expression pattern.

The research was co-led by Olga Troyanskaya, a professor of computer science and the Lewis-Sigler Institute for Integrative Genomics at Princeton, and Matthias Kretzler, a professor of computational medicine and biology at the University of Michigan. The first authors on the study were Wenjun Ju, a research assistant professor at the University of Michigan, and Casey Greene, now at the Geisel School of Medicine at Dartmouth and a former postdoctoral fellow at Princeton.

Explore further: Sex differences in kidney gene expression

More information: Wenjun Ju, Casey S Greene, Felix Eichinger, Viji Nair, Jeffery B Hodgin, Markus Bitzer, Young-suk Lee, Qian Zhu, Masami Kehata, Min Li, Song Jiang, Maria Pia Rastaldi, Clemens D Cohen, Olga G Troyanskaya and Matthias Kretzler. 2013. Defining cell-type specificity at the transcriptional level in human disease. Genome Research. Published in Advance August 15, 2013, DOI: 10.1101/gr.155697.113 , http://genome.cshlp.org/content/early/2013/08/15/gr.155697.113.abstract

Related Stories

Sex differences in kidney gene expression

July 31, 2013
Male and female rats show different patterns of kidney gene expression throughout their lives, a study in the open access journal Biology of Sex Differences reveals. The finding could help explain some of the gender differences ...

Megabladder mouse model may help predict severity of pediatric kidney damage

September 4, 2013
A new study of the megabladder mouse model suggests that tracking changes in the expression of key genes involved in kidney disease could help physicians predict the severity of urinary tract obstruction in pediatric patients, ...

A new method for analyzing gene expression in single cells opens a window into tumors and other tissues

September 22, 2013
A team of researchers affiliated with Ludwig Cancer Research and the Karolinska Institutet in Sweden report in the current issue of Nature Methods a dramatically improved technique for analyzing the genes expressed within ...

Identifying key regulators of kidney injury

May 9, 2013
(Medical Xpress)—Micro-RNAs (miRNAs) are a recently discovered class of RNA molecules that regulate how genes are expressed. UCD researchers led by Conway Fellow, Professor Catherine Godson are studying the role of miRNAs ...

Study of 'sister' stem cells uncovers new cancer clue

September 26, 2013
Scientists have used a brand new technique for examining individual stem cells to uncover dramatic differences in the gene expression levels – which genes are turned 'up' or 'down'– between apparently identical 'sister' ...

Homing in on developmental epigenetics

August 23, 2013
Germ cells have unique molecular features that enable them to perform the important task of transmitting genetic information to the next generation. During development from their embryonic primordial state, germ cells are ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.