Nestin-Expressing Granule Neuron Precursor Cells May Be More Likely to Generate Tumors

Yang-images

Left: Despite expressing Nestin, cultured NEPs (red cells) are committed to generating neurons, which extend characteristic neuronal processes (green fibers). Right: A neonatal mouse cerebellum was stained with fluorescent antibodies to detect neurons and progenitors. Red cells on the surface of the cerebellum are GNPs, and Nestin (green) is found on many progenitors in the cerebellum, including NEPs, rare cells that are prone to give rise to tumors.

The topline

  • Identified a rare population of Nestin-expressing cerebellar precursor cells, called NEPs, which may be more likely to give rise to tumors
  • Findings suggest that intrinsic deficiency in DNA repair capacity can make normal cells tumor-prone

Cerebellar granule neurons, the most abundant neurons in the central nervous system, are usually generated from granule neuron precursors (GNPs) in the external germinal layer (EGL) of a developing cerebellum. However, a team co-led by Fox Chase researcher Zeng-jie Yang, MD, PhD, and Robert Wechsler-Reya, PhD, of Sanford-Burnham Medical Research Institute, recently identified a rare population of cerebellar precursor cells that express Nestin — a protein commonly expressed in multipotent neural stem cells. Although distinct from conventional GNPs — they do not express a signature GNP protein and are usually inactive while GNPs proliferate extensively — these Nestin-expressing progenitors (NEPs) are also dedicated to producing cerebellar granule neurons.

As the researchers described in their October 2013 article in Nature Neuroscience, compared with GNPs, NEPs express much lower levels of genes associated with DNA repair, which protect cells from becoming cancerous. Consistent with this, NEPs exhibit more severe genomic instability and give rise to tumors more efficiently when a cancer-causing mutation occurs.

“Our studies suggest that some properties of tumor cells may not necessarily be the result of somatic mutations, but instead may represent intrinsic characteristics of normal cells at certain stages of development,” the researchers note, highlighting the importance of such characteristics in determining whether and when tumor development will take place. “Identification of ‘tumor-prone’ cell populations may yield new approaches to targeting cancer.”

Zeng-jie Yang, MD, PhD

Yang’s co-authors include Peng Li, PhD, Fang Du, MD, Larra W. Yuelling, PhD, Tiffany Lin, Renata E. Muradimova, MS, Rossella Tricarico, PhD, Jun Wang, PhD, Grigori Enikolopov, PhD, Alfonso Bellacosa, MD, PhD, and Robert J. Wechsler-Reya, PhD.