Determining RNA’s Impact

Gene Yeo’s lab is unraveling stem cell survival, renewal & differentiation

Dr. Gene Yeo 
Sanford Consortium for Regenerative Medicine
UC San Diego

 

Focusing on understanding the impact of RNA processing and regulation in human normal and cancer stem cell biology and neural differentiation. 

Dr. Gene Yeo’s lab at the Sanford Consortium for Regenerative Medicine is a thought leader in single-cell genomics. His lab’s focus is to understand the impact of RNA processing and regulation in human normal and cancer stem cell biology and neural differentiation. Human embryonic stem cells (hESC) are used in the lab as a system for unraveling aspects of stem cell state, such as survival, self-renewal, and differentiation.

The team studies:

  • RNA processing in basic stem cell biology, in particular, the impact of RNA binding proteins and small RNAs during stem cell differentiation.
  • Human disease modeling in induced/embryonic pluripotent stem cells. Understanding the molecular pathways by which induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) transform into neural progenitor cells (NPCs) and mature neurons are vital in developing realistic disease models for human neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s.
  • Development of computational and molecular tools. Vast amounts of binding and splicing-sensitive transcriptome data are becoming readily available and statistical learning theory and generative models are becoming necessary to make sense of the data. In addition, they are developing new molecular capture techniques coupled with high-throughput sequencing for various RNA-related applications.

At the December 2012 American Society of Cell Biology (ASCB) meeting, Dr. Yan Song, a post-doctoral fellow at the YEO LAB, presented a talk entitled: Single Cell Analysis of Induced Pluripotency.

“Our multi-parallel gene profiling studies at single-cell resolution provide important information for studying the heterogeneity of induced pluripotency.”
— Yan Song, Ph.D., YEO LAB

Her talk described the work the lab has done thus far with the C1 Single-Cell Auto Prep System and Biomark HD System. First, they tested the Fluidigm approach to ensure it was reliable and efficient for their research quests. After confirming the approach, they used an embryonic stem cell (ESC) line with GFP+ and Oct4 reporters (developed by the Salk Institute) and treated the stem cells with the 4 Yamanaka factors to switch off the reporters. This became their method for monitoring stem cell states. Third, they ran candidate genes through the ESC model; and finally, they used Principal Component Analysis to begin identifying the roles genes play in the reprogramming process.

“Our multi-parallel gene profiling studies at single-cell resolution provide important information for studying the heterogeneity of induced pluripotency,” Dr. Song said.

Boyko Kakaradov of the YEO LAB contributed the bioinformatics work that went into this presentation.

The team hopes this work will allow them identify more biomarkers to differentiate the various states of the transcription in induced pluripotency stem cells.