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Updated: Jun 16, 2026

Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
Published on: June 10, 2018
Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with
Zhumur Ghosh1, Kitchener D Wilson, Yi Wu
1Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Human induced pluripotent stem cells (hiPSCs) show distinct gene expression compared to human embryonic stem cells (hESCs). Donor cell type significantly impacts hiPSC reprogramming, with fetal fibroblast-derived cells being closest to hESCs.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Genomics
Background:
- Human induced pluripotent stem cells (hiPSCs) offer an alternative to human embryonic stem cells (hESCs), avoiding ethical concerns and immune rejection.
- However, hiPSCs exhibit distinct gene expression patterns compared to hESCs, suggesting incomplete reprogramming.
- The influence of the original tissue type on hiPSC gene expression remains unclear.
Purpose of the Study:
- To investigate the transcriptional profiles of hiPSCs derived from various somatic cell types.
- To assess the degree of reprogramming and the impact of donor tissue origin on hiPSC characteristics.
- To compare hiPSC gene expression with their donor cells and hESCs.
Main Methods:
- Comparative transcriptional profiling of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes.
- Analysis of gene expression patterns in hiPSCs relative to their corresponding donor cells and hESCs.
- Identification of residual donor genes and their regulatory modes in hiPSCs.
Main Results:
- Residual gene expression from the donor cell type significantly contributes to differences between hiPSCs and hESCs, indicating incomplete reprogramming.
- A hierarchy of hiPSC similarity to hESCs was established: fetal fibroblast-derived hiPSCs were closest, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.
- Specific sets of donor genes retained expression in hiPSCs were identified, highlighting the influence of tissue of origin.
Conclusions:
- The tissue of origin plays a crucial role in the reprogramming efficiency and resulting gene expression profile of hiPSCs.
- Understanding donor cell influence is essential for improving hiPSC generation and application in regenerative medicine.
- Fetal fibroblasts represent a promising source for generating hiPSCs with gene expression profiles most similar to hESCs.
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