Abstract：
:Differentiation of human embryonic stem cells into pancreatic β cells holds great promise for the treatment of diabetes. Recent advances have led to the production of glucose-responsive insulin-secreting cells in vitro, but resulting cells remain less mature than their adult primary β cell counterparts. The barrier(s) to in vitro β cell maturation are unclear. Here, we evaluated a potential role for microRNAs. MicroRNA profiling showed high expression of let-7 family microRNAs in vivo, but not in in vitro differentiated β cells. Reduced levels of let-7 in vitro were associated with increased levels of the RNA binding protein LIN28B, a negative regulator of let-7 biogenesis. Ablation of LIN28B during human embryonic stem cell (hESC) differentiation toward β cells led to a more mature glucose-stimulated insulin secretion profile and the suppression of juvenile-specific genes. However, let-7 overexpression had little effect. These results uncover LIN28B as a modulator of β cell maturation in vitro.
journal_name
Stem Cell Reportsjournal_title
Stem cell reportsauthors
Zhou X,Nair GG,Russ HA,Belair CD,Li ML,Shveygert M,Hebrok M,Blelloch Rdoi
10.1016/j.stemcr.2019.11.009subject
Has Abstractpub_date
2020-01-14 00:00:00pages
9-20issue
1issn
2213-6711pii
S2213-6711(19)30412-6journal_volume
14pub_type
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