Universal Markers for hiPSCs Residue Detection

Shi, Hui; Feng, Tiejun; Wang, Rui; Wu, Li-Da; Gu, Yuchun

doi:10.31083/j.fbl2708239

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…On the other hand, we found that non-coding RNA showed better performance. Previous studies reported that ESRG was a robust marker for detecting residuals amongst differentiated cells from three germ lineages 21 and a universal marker to detect hiPSCs residues in different types of hiPSC-derived cells 39 . However, our results demonstrated that ESRG was not specific enough for hCiPSC-islet cells.…”

Section: Discussionmentioning

confidence: 99%

Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers

Wu,

Zhang,

et al. 2023

Sci Rep

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Human pluripotent stem cells (hPSCs) can generate insulin-producing beta cells for diabetes treatment, but residual undifferentiated cells may cause tumors. We developed a highly sensitive assay to detect these cells in islet cells derived from human chemically induced pluripotent stem cells (hCiPSCs), which are transgene-free and safer. We used RNA-seq data to find protein-coding and non-coding RNAs that were only expressed in hCiPSCs, not in islet cells. We confirmed these biomarkers by RT-qPCR and ddPCR. We chose long non-coding RNA (lncRNA) markers, which performed better than protein-coding RNA markers. We found that LNCPRESS2, LINC00678 and LOC105370482 could detect 1, 1 and 3 hCiPSCs in 106 islet cells by ddPCR, respectively. We tested our method on several hCiPSC lines, which could quantify 0.0001% undifferentiated cell in 106 islet cells by targeting hCiPSCs-specific lncRNA transcripts, ensuring the safety and quality of hCiPSC-derived islet cells for clinical use.

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Section: Discussionmentioning

confidence: 99%

Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers

Wu,

Zhang,

et al. 2023

Sci Rep

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Pluripotent stem cell-derived CTLs targeting FGFR3-TACC3 fusion gene in osteosarcoma

Zhan,

Xiao,

Shi

et al. 2024

International Immunopharmacology

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ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations

Laugwitz,

Cheng,

Collins

et al. 2024

Brain

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Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential to aid in the identification of new disease genes and delineate associated phenotypes. Next generation sequencing was performed in seven affected individuals with neurodevelopmental delay and dysmorphic features. Clinical characterization included reanalysis of available neuroimaging datasets and 2D portrait image analysis with GestaltMatcher. The functional consequences of ZSCAN10 loss were modelled in mouse embryonic stem cells (mESC), including a knock-out and a representative ZSCAN10 protein truncating variant. These models were characterized by gene expression and Western blot analyses, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and immunofluorescence staining. Zscan10 knockout mouse embryos were generated and phenotyped. We prioritized bi-allelic ZSCAN10 loss-of-function variants in seven affected individuals from five unrelated families as the underlying molecular cause. RNA-Seq analyses in Zscan10-/- mESCs indicated dysregulation of genes related to stem cell pluripotency. In addition, we established in mESCs the loss-of-function mechanism for a representative human ZSCAN10 protein truncating variant by showing alteration of its expression levels and subcellular localization, interfering with its binding to DNA enhancer targets. Deep phenotyping revealed global developmental delay, facial asymmetry, and malformations of the outer ear as consistent clinical features. Cerebral MRI showed dysplasia of the semicircular canals as an anatomical correlate of sensorineural hearing loss. Facial asymmetry was confirmed as a clinical feature by GestaltMatcher and was recapitulated in the Zscan10 mouse model along with inner and outer ear malformations. Our findings provide evidence of a novel syndromic neurodevelopmental disorder caused by bi-allelic loss-of-function variants in ZSCAN10.

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Universal Markers for hiPSCs Residue Detection

Cited by 3 publications

References 19 publications

Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers

Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers

Pluripotent stem cell-derived CTLs targeting FGFR3-TACC3 fusion gene in osteosarcoma

ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations

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