Chromatin “pre-pattern” and epigenetic modulation in the cell fate choice of liver over pancreas in the endoderm

Abstract

Understanding the basis for multipotency, whereby stem cells and other progenitors can differentiate into certain tissues and not others, provides insights into the mechanism of cell programming in development, homeostasis, and disease. We recently reported a screen of diverse chromatin marks to obtain clues about chromatin states in the multipotent embryonic endoderm. Genetic and pharmacologic tests of certain marks’ function demonstrated that the relevant chromatin modifying factors modulate the fate choice for liver or pancreas induction in the endoderm. The information about chromatin states from embryonic studies can be used to predict lineage-specific developmental potential and chromatin modifiers to enhance particular cell fate transitions from stem cells.

Keywords: :

• Chromatin
• competence
• endoderm
• histone marks
• liver
• pancreas

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Acknowledgments

We thank the members of the Zaret group for advice and comments on the manuscript and ongoing projects, and Eileen Pytko for help in preparing the manuscript. This work was supported by NIH grants R37GM36477 and U01DK072503 to K.S.Z, and K01DK093886 to C.-R.X.