Weaver’s research featured in Cell Stem Cell

Research results from the lab of Valerie Weaver, PhD, were reported online July 21, 2016 in Cell Stem Cell. The article’s title is “Tissue Mechanics Orchestrate Wnt-Dependent Human Embryonic Stem Cell Differentiation.”

Weaver performed her work in the UCSF Department of Surgery. She has a joint appointment in the Department of Bioengineering and Therapeutic Sciences (BTS) and is a core faculty member in the UCSF/UC Berkeley Joint Graduate Program in Bioengineering.

Weaver stated that “A critical aspect of the paper and major mechanism is a soft substrate that enhances cell-cell adhesions and promotes Wnt dependent gene expression by sequestering the transcriptional modifier Kaiso from the nucleus.”

Research summary:

  • Compliant hydrogel substrates enhance mesoderm differentiation of human embryonic stem cells
  • Stabilization of adherens junctions primes human embryonic stem cells for mesoderm differentiation
  • Junctional reorganization and Src activity promote nuclear translocation of β-catenin
  • On stiff gels, β-catenin degradation inhibits mesodermal differentiation

Research significance:

  • Mechanical properties of extracellular matrix substrate are able to profoundly influence stem cell differentiation
  • Tissue mechanics do not drive embryonic stem cell differentiation but instead modify cell responsiveness to exogenous cues
  • Identification of pathways that are involved in translating mechanical cues during embryonic development

The authors are:

  • Laralynne Przybyla, PhD, a postdoctoral fellow in the Weaver lab
  • Johnathon Lakins, PhD, a specialist in the Weaver lab
  • Valerie Weaver, PhD, Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery at UCSF

As an active member of our joint UCSF/UC Berkeley Bioengineering graduate program, Weaver said, “I genuinely enjoy mentoring these talented students.”

“I am extremely proud of Valerie and her colleagues,” said BTS Chair Tejal Desai. “Innovative multidisciplinary research of this caliber inspires all of us and helps us better understand human development and disease.”

About the School: The UCSF School of Pharmacy is a premier graduate-level academic organization dedicated to improving health through precise therapeutics. It succeeds through innovative research, by educating PharmD health professional and PhD science students, and by caring for the therapeutics needs of patients while exploring innovative new models of patient care. The School was founded in 1872 as the first pharmacy school in the American West. It is an integral part of UC San Francisco, a leading university dedicated to promoting health worldwide.