Massachusetts Institute of Technology

Princeton University

Patrick Guye

Ron Weiss

Ihor R Lemischka

Christoph Schaniel

Mohammad Reza Ebrahimkhani

Miles Miller

Priscilla E M Purnick

Priscilla Purnick

Aspects of the present disclosure are directed to methods and compositions for the production of heterogeneous tissue from human induced pluripotent stem (hiPS) cells.

Engineering a heterogeneous tissue from pluripotent stem cells

The present invention provides compositions and methods for programming mammalian cells to perform desired functions. In particular, the present invention provides compositions and methods for programming stem cells to differentiate into a desired cell type. A quorum sensing systems that regulates the expression of cell fate regulators is introduced into mammalian host cells, such as stem cells. The quorum sensing systems generally comprises vectors that express the components of a bacterial quorum sensing pathway, including proteins which catalyze the synthesis of an autoinducer and a gene encoding a regulatory partner of the autoinducer, and vectors in which genes encoding cell fate regulators are operably linked to a promoter induced by the autoinducer/regulatory partner complex. The system can also comprise vectors in which genes encoding additional cell fate regulators are operably linked to a promoter that is induced by a factor synthesized in response to a first stage of differentiation, so that a second stage of differentiation is triggered.

Engineered cellular pathways for programmed autoregulation of differentiation

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Cambridge, MA, United States of America

Patrick Guye