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Millman publishes research characterizing human stem cell-derived islets with multiomics

Jeffrey R. Millman, PhD

On February 27, Jeffrey R. Millman, PhD and collaborators had their research findings published in “bioRxiv,” titled “Multiomic profiling defines cell fate plasticity of in vitro-derived islets.” 

For patients with type 1 diabetes, insulin-secreting β-cells within the pancreatic islets of Langerhans cells are lost. There is limited understanding of the molecular events that govern the process of islets being generated in vitro by human pluripotent stem cell differentiation. 

In this study, Millman and collaborators use single-cell multiomics to define how islets from in vitro differentiation mature. By using this approach “to measure chromatin accessibility and transcriptional profiles of 120,064 cells, they found distinguishing chromatin accessibility and gene expression signatures as well as dynamic profiles for each major islet cell type produced from in vitro differentiation.” 

Chromatin accessibility denoted that β, α, and δ cells from in vitro differentiation had an equivocal cellular identity, and that chromatin accessibility became more defined as time in vitro differentiation elongated or during transplantation into mice. Additionally, “modulation of CTCF expression redirects cell fate from the pancreatic islet endocrine to an intestinal enteroendocrine-like cell type,” and the “knockdown of ARID1B enhances β-cell maturation transcriptionally and by chromatin accessibility.” 

These findings provide great insight for utilizing cell identity and maturation of stem cell-derived islets for therapy and disease modeling. 

Multiomic profiling defines cell fate plasticity of in vitro-derived islets