A novel strategy to generate human iPSCs with enhanced mesodermal and endodermal differentiation capacity.
7 affiliations
- 1Zhejiang Key Laboratory of Signaling Mechanisms in Tumor Progression and Intervention, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
- 2Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China.
- 3Shenzhen Luohu People's Hospital (the Third Affiliated Hospital of Shenzhen University), Shenzhen, 518001, Guangdong, China.
- 4Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China. [email protected].
- 5Shenzhen Beikeyuan Cell Technology Co., Ltd., Shenzhen, China. [email protected].
- 6Zhejiang Key Laboratory of Signaling Mechanisms in Tumor Progression and Intervention, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. [email protected].
- 7Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China. [email protected].
Abstract
Induced pluripotent stem cells (iPSCs) have unlimited proliferative capacity and multi-lineage differentiation potential. Autologous iPSC-derived cells reduce the risk of immune rejection, making them promising resources for regenerative medicine. However, iPSCs derived using conventional methods often show heterogeneity and defects in differentiation potential in a subset of cells. To overcome these limitations, we developed a novel reprogramming strategy, termed the "4CL-primed" strategy, that incorporates a transient early-pluripotency (4CL) treatment during reprogramming. The 4CL-primed iPSCs retained the core characteristics of conventional iPSCs, including normal morphology, pluripotency marker expression, and karyotypic stability, while exhibiting enhanced mesodermal and endodermal differentiation capacity. Furthermore, the cells showed superior performance in directed pancreatic lineage differentiation, generating a higher proportion of pancreatic endocrine β-like cells. Collectively, the 4CL-primed strategy offers a more practical approach for mesodermal and endodermal differentiation research, particularly pancreatic lineage differentiation, thereby providing a more efficient source of pancreatic lineage cells for regenerative medicine and cell-based therapy.
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BibTeX
@article{zhang2026novel,
title = {{A novel strategy to generate human iPSCs with enhanced mesodermal and endodermal differentiation capacity.}},
author = {Mengna Zhang and Ran Zheng and Yujiao Wang and Junjie Wen and Jingyu Xu and Dan Xiao and Yanhong Cheng and Liang Wang and Weifan Cao and Yunfeng Gao and Cheguo Cai},
journal = {Cell regeneration (London, England)},
year = {2026},
month = oct,
doi = {10.1186/s13619-026-00306-9},
url = {https://europepmc.org/article/MED/42905381},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A novel strategy to generate human iPSCs with enhanced mesodermal and endodermal differentiation capacity.
AU - Mengna Zhang
AU - Ran Zheng
AU - Yujiao Wang
AU - Junjie Wen
AU - Jingyu Xu
AU - Dan Xiao
AU - Yanhong Cheng
AU - Liang Wang
AU - Weifan Cao
AU - Yunfeng Gao
AU - Cheguo Cai
PY - 2026
DA - 2026/10/21
JO - Cell regeneration (London, England)
DO - 10.1186/s13619-026-00306-9
UR - https://europepmc.org/article/MED/42905381
AB - Induced pluripotent stem cells (iPSCs) have unlimited proliferative capacity and multi-lineage differentiation potential. Autologous iPSC-derived cells reduce the risk of immune rejection, making them promising resources for regenerative medicine. However, iPSCs derived using conventional methods often show heterogeneity and defects in differentiation potential in a subset of cells. To overcome these limitations, we developed a novel reprogramming strategy, termed the "4CL-primed" strategy, that incorporates a transient early-pluripotency (4CL) treatment during reprogramming. The 4CL-primed iPSCs retained the core characteristics of conventional iPSCs, including normal morphology, pluripotency marker expression, and karyotypic stability, while exhibiting enhanced mesodermal and endodermal differentiation capacity. Furthermore, the cells showed superior performance in directed pancreatic lineage differentiation, generating a higher proportion of pancreatic endocrine β-like cells. Collectively, the 4CL-primed strategy offers a more practical approach for mesodermal and endodermal differentiation research, particularly pancreatic lineage differentiation, thereby providing a more efficient source of pancreatic lineage cells for regenerative medicine and cell-based therapy.
SN - 2045-9769
ER -