Molecular Elucidation and Engineering of the Stem Cell Fate Decisions

Molecular
Elucidation and Engineering of the Stem Cell Fate Decisions


David Schaffer, Ph.D.

Professor of Chemical and Biomolecular Engineering, Bioengineering, and the
Helen Wills Neuroscience Institute

Director,
Berkeley Stem Cell Center

University
of California, Berkeley, CA, USA, 94720-3220

Elucidating the mechanisms that govern stem cell self-renewal and
differentiation is critical for understanding the roles these cells play in organismal
development and function as well as for harnessing stem cells to repair tissues
damaged by disease or injury.  It has
become increasingly clear that stem cells are regulated not only by biochemical
signals in the niche, but also by biophysical features in the way these signals
are presented, though investigating the latter is challenged by experimental
complexities in investigating and mimicking the complexity of the extracellular
matrix (ECM), cell-cell interactions, and other niche components.  Recent work has demonstrated that bioactive,
synthetic materials can be harnessed to emulate and thereby study the effects
of solid phase, biophysical cues on cell function.  For example, activation of many cellular receptors involves
the formation of oligomeric protein signaling complexes with ligands presented
from the matrix, the surface of neighboring cells, and in some cases even from
solution.  We have developed
multivalent ligands – polymers conjugated to signaling proteins to yield
biomimetic signals with nanoscale spatial organization – which potently induce
the differentiation of human pluripotent stem cells in vitro and neural stem
cells in vitro and in vivo.  In
addition, these materials combined with optogenetics and super-resolution
microscopy have yielded insights into signaling mechanisms that regulate the
fate decisions of these cells. 
Finally, such biomimetic materials can be integrated into safe, scaleable,
and robust bioprocesses for pluripotent stem cell expansion and differentiation.