Assistant professor Chong Shin and members of her lab discovered Fhl1b as a novel target of Bone morphogenetic protein (Bmp) signaling. Bmp signaling has been shown to play an essential role in inducing the liver at the expense of pancreas in different animal models. Nevertheless, the identity of downstream gene regulatory networks of Bmp signaling that specify the liver to the detriment of pancreas remains elusive. Moreover, the key question of whether Bmp signaling suppresses pancreas gene program keeping progenitors competent to differentiate into the liver or directly induces the liver gene program has not yet been answered.

Using transcriptome profiling and single-cell level functional analyses in a zebrafish model, Shin and colleagues have discovered Fhl1b as a Bmp2b signaling target that may actively suppress the pancreas gene program to properly modulate liver induction, lineage allocation, and β-cell regeneration.

These findings of Bmp2b regulation of Fhl1bsuggest a new paradigm of how Bmp signaling regulates the cell fate choice of liver versus pancreas and β-cell mass. Furthermore, these results give profound insight into why effective Bmp signaling suppression is critical for the induction β-cells in human pluripotent stem cells (hESCs). Accordingly, a comprehensive understanding of how lineage-specific multipotent progenitors make a developmental choice will shed light on the re/programming of stem/progenitor cells into specific cell lineages, enabling us to generate functionally relevant cells for clinical utility.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK081351), the Regenerative Engineering and Medicine Research Center (GTEC 2731336 and GTEC 1411318), the National Science Foundation (1354837), and the School of Biology (Georgia Institute of Technology).

Citation: Xu J, Cui J, Del Campo A, Shin CH (2016) Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration. PLoS Genet 12(2): e1005831. doi:10.1371/journal.pgen.1005831