Events

Martina Koeva

Biomolecular Engineering, UCSC
Stemness revisited: a meta-analysis of stem cell signatures using high-throughput gene expression data integration

Monday, November 16, 2009, 4:00 pm
305 Physical Sciences Building

Dissertation defense: Stem cells are functionally defined cells with a high therapeutic potential for many diseases. The stemness hypothesis states that stem cells share a core set of mechanisms that regulate the shared stem cell properties of self-renewal and multi-lineage potential. Previous attempts to identify genes required for core stem cell function across stem cell types using transcriptional profiling have identified few such genes.  My work focuses on the development of a computational stemness meta-analysis (SMA) method that uses high-throughput differential gene expression data integration to address three main questions: do functional redundancy and tissue-specific expression mask common molecular mechanisms shared between stem cell types? Are stemness mechanisms conserved between mouse and human stem cells? Can we use gene expression signatures to predict stem cell state?

The SMA method identified 103 mouse evolutionarily related groups of homologous genes with reproducible, statistically significant, cell type diverse and stem cell-specific upregulation in multiple stem cell types. The results point to specific examples of functional redundancy in modules controlling cell adhesion, quiescence, and gene silencing. Shared homolog modules also include genes in the Myc, Myb, Chd, Hspa, Id, and many other families. Genes within the stemness homolog families are prime candidate regulators of conserved stemness mechanisms and may play critical roles as stem cell markers.

I measured the level of conservation of stemness mechanisms between mouse and human cells. Application of the SMA method to a human stem cell compendium indicates that human data are globally more heterogeneous than murine stem cell data. However, human stemness families incorporate several conserved mammalian stemness modules, such as the Integrin alpha, TCF/LEF, Frizzled, Notch, and Chd families.

Finally, I used the stemness modules identified in the mouse SMA to define a stemness index score and evaluate how stem cell-like a new gene expression signature is. I validated the predictiveness of the stemness modules through an internal cross-validation test and applied the stemness index test to a large set of new experiments from normal stem cells, side populations, cancer stem cells, and metastatic populations. The results indicate that mouse stemness modules could predict stem cell-like features in various data sources with high accuracy and give clues into disease mechanisms.

Advisor: Josh Stuart

UCSC Stem Cell Journal Club

This journal club for the UCSC CIRM training program is open to anyone interested in stem cell research. The program is a roundtable format, so please read the paper beforehand and come prepared to discuss it.

See the schedule and information about the paper being reviewed
599 Engineering 2
UC Santa Cruz
12:00-1:30 pm
Refreshments served

Sponsors:
UCSC CIRM Training Program in Systems Biology of Stem Cells
California Institute for Quantitative Biosciences (QB3)
Millipore

Bay Area Stem Cell Club

The Bay Area Stem Cell Club promotes interactions, collaborations, and scientific exchange among stem cell scientists in the Bay Area. Participation is open to all interested parties, but only students and post-docs present their work.

Thursday, December 3, 2009
4:00-6:00 pm, scientific program
6:00-7:00 pm, social hour, drinks and appetizers
UCSF Mission Bay Campus
Genentech Hall Auditorium, 1st Floor
600 16th Street, San Francisco
Directions and parking info

Presentations:
Introduction, Dan Lim, UCSF
Who’s in CHARGE: chromatin remodelers in craniofacial
development
Ruchi Bajpai, Joanna Wysocka Lab, Stanford
Switching of the core transcription machinery during hepatic
development
Tony D’Alessio, Robert Tijan Lab, UC Berkeley
Inhibitory neuron transplantation induces plasticity after the
critical period
Sunil Gandhi, Michael Stryker Lab, UCSF
The role of stem cell-secreted VEGF in functional recovery and
brain repair after stroke
Tonya Bliss, Gary Steinberg Lab, Stanford

Contacts: Dan Lim, (415) 353-3489, or Erica Stidham,