Single nuclei multiomics of human stem cell-derived islets identifies deficiencies in lineage specification. Single nuclei multiomics of human stem cell-derived islets identifies deficiencies in lineage specification

We profiled the transcritpome and ATAC profiles of human pancreatic islets generated from pluripotent stem cells. Multiomic profiling was also performed on primary human islets and in vivo matured SC-islets for comparision. We catalogued the ATAC associated signatures for each cell types in SC-islets and compared them to their human primiary islet counterparts. In vivo maturation of SC-islets were also compared with in vitro SC-islets. In this study, we identified key regulators associated with islet identity during differentiation and maturation. Gene manipulation of CTCF affects differentiating SC-islet cell fate to enteroendocrine-like lineage. ARID1B knockdown caueses islet cells to present mature signatures. These gene altered SC-islets were also sequenced. Overall design: Single nulei multiome (RNA and ATAC) sequencing of human islets and stem cell derived islets.