Templated Pluripotent Stem Cell Differentiation via Substratum-Guided Artificial Signaling

Area of Science:

• Synthetic biology
• Developmental biology
• Biomaterials science

Background:

• Synthetic morphogenesis uses synthetic biology to understand minimal cellular processes in development.
• Existing tools lack precision for studying molecular mechanisms in cell fate patterning during morphogenesis.
• Pluripotent stem cells (PSCs) are crucial for developmental studies but require advanced manipulation tools.

Purpose of the Study:

• To present a novel platform, PSC-MATRIX, for artificial signaling in PSCs.
• To enable spatiotemporal control of developmental events through programmable biomaterials.
• To investigate molecular mechanisms driving PSC differentiation and cell fate acquisition.

Main Methods:

• Combining cell engineering with biomaterial design for PSCs.
• Utilizing synthetic Notch (synNotch)-engineered human PSCs.
• Implementing orthogonal signaling pathways with materials and ligands (e.g., green fluorescent protein).

Main Results:

• PSC-MATRIX demonstrated temporal and spatial control of transgene expression for up to 11 days.
• The platform successfully regulated multiple differentiation events in engineered PSCs.
• Material-mediated signaling via orthogonal ligands controlled cell fate acquisition.

Conclusions:

• The PSC-MATRIX platform provides a synthetic approach to interrogate PSC differentiation mechanisms.
• This tool facilitates probing and guiding cell fate acquisition in a controlled manner.
• The platform has broad applicability across various stem cell differentiation protocols.