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Small‐molecule modulators of Nkx6.1 expression in pancreatic progenitor cells during directed differentiation of human embryonic stem cell to insulin producing beta cells
Author(s) -
Peterson Quinn,
Melton Douglas
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.2
Subject(s) - progenitor cell , embryonic stem cell , microbiology and biotechnology , stem cell , beta cell , cellular differentiation , directed differentiation , biology , transplantation , chemistry , medicine , endocrinology , insulin , induced pluripotent stem cell , islet , biochemistry , gene
Type 1 diabetes is characterized by destruction of the insulin‐producing pancreatic beta cells, resulting in dysregulation of blood glucose levels. As such, the identification of small‐molecules capable of efficiently inducing the differentiation of human embryonic stem cells (hESC) to insulin producing beta cells may provide a route to cell transplantation therapies for these patients. In 2012, several protocols were reported to generate pancreatic precursor cells capable of further differentiation into beta cells when transplanted into mice. However, these pancreatic precursors do not generate functional beta cells in vitro . One possible explanation of this effect is the absence of the critical pancreatic progenitor transcription factor, Nkx6.1, in over 60% of the hESC derived pancreatic progenitor cells in vitro . Thus incomplete induction of Nkx6.1 may represent a barrier to beta cell production in vitro . To this end, we sought to uniformly induce Nkx6.1 expression in pancreatic progenitors. Herein, we report the development of a combinatorial screening platform for the identification of small‐molecules that can induce Nkx6.1 expression in pancreatic precursor cells, and the elucidation of pathways driving this aspect of beta cell differentiation.