CHI’s XGen Congress 2010 kicked off this week, bringing folks interested in Epigenetics, NGS, CNV, qPCR and Data Analysis & Storage all together in sunny San Diego for the event. The Epigenetics track featured a powerhouse lineup of speakers including: Peter Jones, Michelle Barton, Mike Witcher, Kevin Morris, David Hawkins and Kun Zhang and one of our favorite talks featuring Guoping Fan .
Featured Talk: DNA Methylation in Cell Differentiation and Reprogramming
Guoping Fan, UCLA
Dr. Fan first focused on the role of DNAm in differentiation and development. He explained how DNA methylation was crucial in developmental gene regulation, genomic imprinting, X-inactivation, and genome stability. He then discussed his work on DNA methyltranferases in mice, showing how mutations of DNMT1, DNMT3a, and DNMT3b lead to a lethal phenotype. His just released paper shows how DNMT1 and 3a maintain DNA methylation in mouse brains, illustrated by knockout experiments where loss of DNMT1 and 3a leads to cortical degeneration.
A few other interesting points from this section were:
- During transition from hESCs into neural precursor cells (NPCs), a subset of CpG island promoters undergo de novo methylation during the differentiation and expansion of hESC-derived NPCs
- Based on its expression pattern in hESC differentiation, DNMT3A is likely the major enzyme involved in CpG island methylation during hESC differentiation
- A small number of genes show abnormally higher levels of CpG island methylation in late passages of NPCs, which leads to abnormal silencing of gene transcription.
Cellular reprogramming and induced pluripotent stem cells (iPSCs) studies have been blowing up lately . A $1M question: How similar are iPSCs to actual embryonic stem cells (hESCs)? Dr. Fan’s group tackled that question by profiling DNA methylation in several lines of iPSCs and hESCs, all compared to somatic cells. Here are the results that they passed along:
- Approximately 6-14% of genes exhibit changes in promoter methylation during the conversion of human somatic cells into iPSCs
- Many more genes undergo de novo methylation than demethylation during cell reprogramming
- A unique methylation signature in iPSCs can serve as a biomarker to distinguish iPSCs from both somatic cells and hESCs
- Many hypermethylated genes in iPSCs are involved in specialized cellular function such as epidermal cell differentiation.
Check out the latest research from Guoping Fan’s team for yourself in Nature Neuroscience, March 2010.