Single-Cell Analysis Changes Understanding of Organ Development
Researchers examining early kidney development used a recently developed single cell RNA-sequence strategy to create a new atlas of gene expression patterns that has already led to a significant finding on the nature of organ development.
The study, published in August 2014 in the journal Development, included senior author Steven Potter, PhD, Division of Developmental Biology; Joo-Seop Park, PhD, Division of Urology, and research associate Eunah Chung. The study reports that during organogenesis in mice, single cells often express genes related to several developmental pathways – not just a single, predetermined fate. This finding provides powerful evidence of a concept called multilineage priming.
During early development, cells partially activate multiple programs, priming them for their next step in development. This is followed by a combination of gene repressions, which turn off the genes associated with various possible lineages until each cell settles upon its ultimate state. “This was a surprise,” Potter says. “We had expected that cells would just gradually fire up the correct program as they assumed their differentiated state.”
The team also was surprised to see an abundance of genes with partially degraded noncoding RNA. All these findings are changing our understanding of early organ development, which in turn could lead to new ways to treat or prevent disease.
“As is common in science, this new data raises new questions,” Potter says. “How do cells decide which programs to test and how do they make their final decisions? We do not yet know, but new knowledge brings new power. We are moving steadily forward in our quest for groundbreaking therapeutic options.”
