PDX1+ cell budding morphogenesis in a stem cell-derived islet spheroid system

Jia Zhao (), Shenghui Liang, Haoning Howard Cen, Yanjun Li, Robert K. Baker, Balwinder Ruprai, Guang Gao, Chloe Zhang, Huixia Ren, Chao Tang, Liangyi Chen, Yanmei Liu, Francis C. Lynn, James D. Johnson and Timothy J. Kieffer ()
Additional contact information
Jia Zhao: University of British Columbia
Shenghui Liang: University of British Columbia
Haoning Howard Cen: University of British Columbia
Yanjun Li: Peking University
Robert K. Baker: University of British Columbia
Balwinder Ruprai: University of British Columbia
Guang Gao: University of British Columbia
Chloe Zhang: University of British Columbia
Huixia Ren: Peking University
Chao Tang: Peking University
Liangyi Chen: Peking University
Yanmei Liu: South China Normal University
Francis C. Lynn: University of British Columbia
James D. Johnson: University of British Columbia
Timothy J. Kieffer: University of British Columbia

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50109-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50109-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50109-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().