Revealing transcription factors during human pancreatic β cell development

Abstract

Developing cell-based diabetes therapies requires examining transcriptional mechanisms underlying human β cell development. However, increased knowledge is hampered by low availability of fetal pancreatic tissue and gene targeting strategies. Rodent models have elucidated transcription factor roles during islet organogenesis and maturation, but differences between mouse and human islets have been identified. The past 5 years have seen strides toward generating human β cell lines, the examination of human transcription factor expression, and studies utilizing induced pluripotent stem cells (iPS cells) and human embryonic stem (hES) cells to generate β-like cells. Nevertheless, much remains to be resolved. We present current knowledge of developing human β cell transcription factor expression, as compared to rodents. We also discuss recent studies employing transcription factor or epigenetic modulation to generate β cells.

Keywords: diabetes mellitus; epigenetics; human; organogenesis; transcription factor.

Figure 1

Approximate timeline of transcription factor expression during human β cell development. A relative course of human and mouse β cell development is depicted. Transcription factors (in shaded boxes) are listed under each time-point where their expression is first observed, or lost, according to the literature. For comparison, approximate mouse developmental points are included under the human timeline. Early [i.e., pancreatic budding and multipotent pancreatic progenitor cell (MPC) formation] and late (i.e., lineage specification and β cell maturation) stages of pancreas formation are approximated by labels and dashed boxes. Some transcription factors are marked with an *, denoting that whole pancreas mRNA was used to characterize expression, thus cell type-specificity was not determined. Transcription factors with arrows extending denote expression that persists into postnatal and/or mature β cells. Abbreviations: E, embryonic day; W, weeks gestation.