| Autor: |
Zhao, Jia, Liang, Shenghui, Cen, Haoning Howard, Li, Yanjun, Baker, Robert K., Ruprai, Balwinder, Gao, Guang, Zhang, Chloe, Ren, Huixia, Tang, Chao, Chen, Liangyi, Liu, Yanmei, Lynn, Francis C., Johnson, James D., Kieffer, Timothy J. |
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| Zdroj: |
Nature Communications; 7/13/2024, Vol. 15 Issue 1, p1-18, 18p |
| Abstrakt: |
Remarkable advances in protocol development have been achieved to manufacture insulin-secreting islets from human pluripotent stem cells (hPSCs). Distinct from current approaches, we devised a tunable strategy to generate islet spheroids enriched for major islet cell types by incorporating PDX1+ cell budding morphogenesis into staged differentiation. In this process that appears to mimic normal islet morphogenesis, the differentiating islet spheroids organize with endocrine cells that are intermingled or arranged in a core-mantle architecture, accompanied with functional heterogeneity. Through in vitro modelling of human pancreas development, we illustrate the importance of PDX1 and the requirement for EphB3/4 signaling in eliciting cell budding morphogenesis. Using this new approach, we model Mitchell-Riley syndrome with RFX6 knockout hPSCs illustrating unexpected morphogenesis defects in the differentiation towards islet cells. The tunable differentiation system and stem cell-derived islet models described in this work may facilitate addressing fundamental questions in islet biology and probing human pancreas diseases. The ability to differentiate human pluripotent stem cells (hPSCs) into insulin producing cells holds potential for diabetes treatments, but many of these approaches lack the complexity needed for in vitro disease modeling. Here they develop an hPSC-derived islet spheroid system, offering an experimental model to study pancreatic budding and islet morphogenesis with human cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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