A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and post...

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Main Authors: Tongran Zhang, Nannan Wang, Zhiying Liao, Jingyi Chen, Hao Meng, Haopeng Lin, Tao Xu, Lihua Chen, Ling-Qiang Zhu, Huisheng Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2024.1490040/full
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author Tongran Zhang
Tongran Zhang
Nannan Wang
Nannan Wang
Zhiying Liao
Zhiying Liao
Jingyi Chen
Jingyi Chen
Hao Meng
Hao Meng
Haopeng Lin
Tao Xu
Tao Xu
Lihua Chen
Lihua Chen
Ling-Qiang Zhu
Huisheng Liu
Huisheng Liu
Huisheng Liu
Huisheng Liu
author_facet Tongran Zhang
Tongran Zhang
Nannan Wang
Nannan Wang
Zhiying Liao
Zhiying Liao
Jingyi Chen
Jingyi Chen
Hao Meng
Hao Meng
Haopeng Lin
Tao Xu
Tao Xu
Lihua Chen
Lihua Chen
Ling-Qiang Zhu
Huisheng Liu
Huisheng Liu
Huisheng Liu
Huisheng Liu
author_sort Tongran Zhang
collection DOAJ
description In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.
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language English
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publisher Frontiers Media S.A.
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spelling doaj-art-cad4d229a56d4bdeb54fb65e41d30b162025-08-20T01:47:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-10-011210.3389/fcell.2024.14900401490040A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cellsTongran Zhang0Tongran Zhang1Nannan Wang2Nannan Wang3Zhiying Liao4Zhiying Liao5Jingyi Chen6Jingyi Chen7Hao Meng8Hao Meng9Haopeng Lin10Tao Xu11Tao Xu12Lihua Chen13Lihua Chen14Ling-Qiang Zhu15Huisheng Liu16Huisheng Liu17Huisheng Liu18Huisheng Liu19Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaCollege of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Testing and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaCollege of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, ChinaSchool of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, ChinaIn this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fcell.2024.1490040/fullhPSCsstem cell differentiationpancreatic delta cellsFGFislet organoids
spellingShingle Tongran Zhang
Tongran Zhang
Nannan Wang
Nannan Wang
Zhiying Liao
Zhiying Liao
Jingyi Chen
Jingyi Chen
Hao Meng
Hao Meng
Haopeng Lin
Tao Xu
Tao Xu
Lihua Chen
Lihua Chen
Ling-Qiang Zhu
Huisheng Liu
Huisheng Liu
Huisheng Liu
Huisheng Liu
A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
Frontiers in Cell and Developmental Biology
hPSCs
stem cell differentiation
pancreatic delta cells
FGF
islet organoids
title A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
title_full A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
title_fullStr A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
title_full_unstemmed A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
title_short A differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
title_sort differentiation protocol for generating pancreatic delta cells from human pluripotent stem cells
topic hPSCs
stem cell differentiation
pancreatic delta cells
FGF
islet organoids
url https://www.frontiersin.org/articles/10.3389/fcell.2024.1490040/full
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