Timing is everything: gene rhythm determines brain cell fate

November 1, 2013

Scientists at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) may have uncovered how neural progenitor cells (NPCs) -- also known as neural stem cells --in the brain decide their fate.

"NPCs possess the special ability to develop into specific cell types in the brain such as neurons, oligodendrocytes, and astrocytes," said Itaru Imayoshi, an author involved in the study. "These cells relay signals, protect neurons from damage, and aid in repair after injury. However, it is unclear what happens to genes while NPCs transform. "

In a report published in Science, the team of researchers, headed by Ryoichiro Kageyama, studied the activation frequency and pattern of three genes -- Ascl1, Hes1, and Olig2 --in mouse NPCs.

"We observed that when these genes were being turned on every three to eight hours, NPCs tended to stay in a plastic-like state, maintaining their ability to morph into other cell types," explained Imayoshi. "However, when NPCs committed to specific cell fates, the activation continued to increase for over several hours, which suggested the rhythm of gene activation may be important for controlling NPCs."

To test if this was indeed the case, the researchers used engineered cells to selectively turn on and control genes by light. Similar to their initial observations, the frequency of gene activation was key. Short intervals, when the genes were turned on, maintained NPCs while extended activation periods drove the NPCs to change into distinct cell types.

"Not only does this study reveal the dynamics of genes controlling NPC fate, it may also provide an efficient way to control stem cells using light," said Kageyama.

Publication Information

Extenal LinkOscillatory Control of Factors Determining Multipotency and Fate in Mouse Neural Progenitors


Itaru Imayoshi1-4,*,†, Akihiro Isomura1,5,†, Yukiko Harima1,5, Kyogo Kawaguchi6, Hiroshi Kori5,7, Hitoshi Miyachi1, Takahiro Fujiwara3, Fumiyoshi Ishidate3, and Ryoichiro Kageyama1,3,5,*

Science | Published 6 December 2013 | DOI: 10.1126/science.1242366

  1. Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, Japan.
  2. The Hakubi Center, Kyoto University, Kyoto 606-8302, Japan.
  3. World Premier International Research Initiative-Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
  4. Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
  5. Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
  6. Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
  7. Department of Information Sciences, Ochanomizu University, Tokyo 112-8610, Japan.

*Corresponding author.
†These authors contributed equally to this work.