AGTC Genomics Advances Tissue Engineering and Regenerative Medicine Through Multi Omics Analyses
Scientific session at DTERM UKM examines genomic integrity, transcriptional heterogeneity and epigenetic regulation in stem cells and engineered tissues
AGTC Genomics highlighted the application of integrated genomics, transcriptomics and epigenomics to tissue engineering and regenerative medicine during a scientific meeting at the Department of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM).
For researchers developing stem-cell-derived products and engineered tissues, a central challenge is linking genetic integrity with biological function. Integrating next-generation sequencing (NGS) with bioinformatics and experimental validation can help distinguish donor-associated variation, culture adaptation and incomplete differentiation, strengthening the interpretation and reproducibility of regenerative research.
Genomic assessment from donor material to expanded cell populations
Genomic profiling can establish a baseline for donor-derived cells, authenticate cell lines and identify variants relevant to the proposed research or therapeutic application. Comparison with original donor material helps distinguish pre-existing variants from alterations detected after reprogramming, expansion or differentiation. Donor assessment also requires clinical information, infectious-disease screening and consent addressing genetic analyses and potentially significant findings. [1]
Genomic stability requires longitudinal assessment because culture can both generate new alterations and select pre-existing minor clones. Master and working cell banks, major manipulation steps and subsequent passages provide informative sampling points. For human pluripotent stem cells, recurrent abnormalities include gains affecting chromosomes 12, 17 and 20, focal copy-number changes and cancer-associated variants such as TP53 mutations. These changes can influence proliferation, survival and differentiation, potentially confounding experimental results. [2]
Whole-genome sequencing offers broad interrogation of sequence and structural variation; whole-exome sequencing concentrates on coding regions; targeted deep sequencing can increase sensitivity at selected loci. Assay choice should reflect the variant classes and mosaic fractions of interest. Complementary chromosome analysis and orthogonal confirmation remain important because no single method captures all abnormalities. A negative result must be interpreted against coverage, sampling and the validated limit of detection. [2]
Resolving cellular identity and differentiation through transcriptomics
Bulk RNA sequencing enables differential-expression and pathway analyses across donors, culture conditions and differentiation stages. In human pluripotent stem-cell systems, expression programmes involving POU5F1 (OCT4), SOX2 and NANOG can be examined alongside lineage-associated genes and developmental reference profiles. Such analyses help assess the undifferentiated state and lineage commitment; expression of these markers alone does not establish functional pluripotency. [3]
Single-cell RNA sequencing resolves population heterogeneity that bulk measurements can obscure. It can distinguish progenitors, intended derivatives and off-target populations, and support inference of differentiation trajectories. This is valuable for evaluating whether a protocol changes cell-state composition or transcriptional activity within a defined population. Computational trajectories represent inferred relationships rather than direct lineage tracing, and rare-population detection depends on sampling and assay performance. [4]
Interrogating epigenetic regulation and developmental competence
DNA methylation profiling and chromatin-accessibility assays such as ATAC-seq provide complementary information on regulatory state. Integrated RNA and chromatin analyses can associate transcriptional programmes with accessible regulatory elements and candidate transcription-factor networks. Methylation analyses can investigate incomplete reprogramming, imprinting abnormalities and residual donor-cell epigenetic memory, features that may contribute to variation in differentiation propensity between cell lines. [4,5,7]
The objective is to relate molecular identity to functional competence. Evidence of an undifferentiated state must be distinguished from demonstrated self-renewal and differentiation capacity, while tissue-specific identity must be connected to relevant functional assays. Molecular signatures support mechanistic interpretation and candidate potency-marker discovery; establishing a potency assay requires validation against the intended biological activity. [3]
International studies demonstrate practical research applications
At Harvard University and the Broad Institute of MIT and Harvard, Merkle and colleagues sequenced the exomes of 140 human embryonic stem-cell lines. Their 2017 Nature study identified dominant-negative TP53 mutations in five unrelated lines and demonstrated increasing mutant allele fractions during culture. These findings established that cancer-associated clones can gain a selective advantage, supporting genetic assessment beyond morphology and conventional phenotypic characterisation. [6]
Researchers at Kyushu University, Kyoto University and RIKEN subsequently used whole-genome bisulfite sequencing to characterise iPSC-derived retinal pigment epithelial cells associated with the first autologous iPSC-based transplantation programme. Their 2019 Stem Cell Reports study found broad resemblance to native retinal pigment epithelium alongside persistent methylation abnormalities, including imprinting and reprogramming-associated differences. The functional implications remained unresolved, illustrating the need to connect epigenomic findings with biological validation. [5]
In 2026, Barbara Treutlein’s group at ETH Zurich and collaborators reported paired single-cell transcriptome and chromatin-accessibility sequencing of midbrain and hindbrain organoids in Nature Neuroscience. Integrating regulatory-network inference, transcription-factor perturbation and morphogen screening identified conditions promoting specific neuronal populations. This study illustrates how multi-omics can guide experimental design and differentiation-protocol refinement. [4]
Supporting reproducible tissue engineering research in Malaysia
For tissue engineering laboratories, these approaches could support controlled comparisons of biomaterials, scaffold properties, culture media and differentiation protocols. Profiling across biological replicates and time points can help separate donor effects from experimental effects, identify candidate regulatory mechanisms and benchmark engineered tissues against appropriate reference populations. Functional measurements remain necessary to establish whether molecular changes improve the intended tissue properties.
Through the session at DTERM UKM, AGTC Genomics shared how sequencing and integrated bioinformatics can contribute to this research workflow. Combining genomic surveillance with transcriptional and epigenetic characterisation provides a stronger basis for investigating cellular behaviour, optimising experimental protocols and generating evidence for subsequent translational development.
About AGTC Genomics
AGTC Genomics is a Malaysian genomics company providing molecular diagnostics, sequencing and bioinformatics services for healthcare and research. Its capabilities include whole-genome and whole-exome sequencing, bulk and single-cell transcriptomics, and epigenomic profiling. Operating from its advanced genomics laboratory in Kuala Lumpur, the company holds ISO 15189, ISO/IEC 17025 and College of American Pathologists (CAP) accreditations.
References
1. ISSCR. Basic Characterization; Guidelines for Stem Cell Research and Clinical Translation. https://www.isscr.org/basic-research-standards/basic-characterization ; https://pmc.ncbi.nlm.nih.gov/articles/PMC8190668/
2. ISSCR. Genomic Characterization. https://www.isscr.org/basic-research-standards/genomic-characterization
3. ISSCR. Pluripotency and the Undifferentiated State. https://www.isscr.org/basic-research-standards/pluripotency
4. Azbukina N et al. Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering. Nature Neuroscience. 2026;29:1548–1558. doi:10.1038/s41593-026-02316-x.
5. Araki H et al. Base-Resolution Methylome of Retinal Pigment Epithelial Cells Used in the First Trial of Human Induced Pluripotent Stem Cell-Based Autologous Transplantation. Stem Cell Reports. 2019;13:761–774. doi:10.1016/j.stemcr.2019.08.014.
6. Merkle FT et al. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature. 2017;545:229–233. doi:10.1038/nature22312.
7. Kim K et al. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nature Biotechnology. 2011;29:1117–1119. doi:10.1038/nbt.2052.
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