Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines

Chang, Eun Ah; Tomov, Martin L.; Suhr, Steven T.; Luo, Jiesi; Olmsted, Zachary T.; Paluh, Janet L.; Cibelli, José B.

doi:10.1038/srep15234

Cited by 36 publications

(50 citation statements)

References 12 publications

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“…ED-iPSC lines H3.1.1 as well as A2.2.2 for example, differentiated into all cell types tested in this study including contractile cardiomyocytes, and all of these ED-iPSC lines were previously validated by teratoma formation, qRT-PCR of pluripotency biomarkers, and tri-lineage commitment (Table 1 and Ref. 13). The slightly different epigenomic states, are expected to arise as a result of stochastic complexity in reprogramming17, and identify genes and pathways present as starting points for pluripotency and multi-lineage differentiation.…”

Section: Resultsmentioning

confidence: 95%

“…We examined differentiation to smooth muscle and cardiomyocytes from mesoderm committed Brachyury-T positive lines A2.2.2, F3.5.2, and H3.3.1 (ref. 13; Figs 1d and 3a,b) using established protocols (refs 42, 43, 44, 45; Sciencell Research Laboratories, Carlsbad, CA) and compared to hESC line WA09 (H9, Fig. 3c).…”

Section: Resultsmentioning

confidence: 99%

“…The ED-iPSC lines analyzed in this study fit this need and include replicate lines of Asian or of Hispanic-Latino designation that were derived from fibroblasts and analyzed under a single platform. In addition, we initiate differentiation protocols from lithography templated uniform EBs to increase accuracy of our comparative analysis132223. In our initial validation of these ED-iPSC cell lines we confirmed normal karyotype, verified pluripotency biomarkers by qRT-PCR, and confirmed teratoma formation as well as in vitro tri-lineage commitment, summarized here in Table 1.…”

mentioning

confidence: 84%

“…Stochastic epigenomic differences fall into two primary clusters, each capable of pluripotency as gauged by teratoma and qRT-PCR13 as well as our new data on multi-lineage differentiation into pyramidal neurons, CD44+/GFAP+ astrocytes, RPE cells, pancreatic progenitors, smooth muscle and contractile cardiomyocytes. We use previously established protocols for differentiation and initiate differentiation from custom templated uniformly sized EB intermediates for consistency in comparative analysis2223.…”

mentioning

confidence: 88%

“…The growing number of potential therapeutic applications of iPSCs include high impact diseases, related to cardiac health7 spinal muscular atrophy8, neurodegeneration910 and Type I diabetes11. Investigation into natural variations based on gender, age and ethnicity and how these contribute to disease and therapeutic outcomes are receiving increased attention that is possible now through inclusion of these parameters in new stem cell resources1213141516. Most challenging to iPSC technology is perhaps ethnic diversity and the additional complexity it brings in distinguishing reprogramming versus ethnic-specific contributions to the generation of multiple functional cells or tissues, which has not yet been investigated.…”

mentioning

confidence: 99%

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Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Tomov

Olmsted

Dogan

et al. 2016

Sci Rep

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The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. When possible, population diversity should be included in new studies as resources become available. Previously we derived replicate iPSC lines of African American, Hispanic-Latino and Asian self-designated ethnically diverse (ED) origins with normal karyotype, verified teratoma formation, pluripotency biomarkers, and tri-lineage in vitro commitment. Here we perform bioinformatics of RNA-Seq and ChIP-seq pluripotency data sets for two replicate Asian and Hispanic-Latino ED-iPSC lines that reveal differences in generation of contractile cardiomyocytes but similar and robust differentiation to multiple neural, pancreatic, and smooth muscle cell types. We identify shared and distinct genes and contributing pathways in the replicate ED-iPSC lines to enhance our ability to understand how reprogramming to iPSC impacts genes and pathways contributing to cardiomyocyte contractility potential.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 84%

mentioning

confidence: 88%

mentioning

confidence: 99%

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Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Tomov

Olmsted

Dogan

et al. 2016

Sci Rep

Self Cite

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In Situ Hydrogelation of Cellular Monolayers Enables Conformal Biomembrane Functionalization for Xeno‐Free Feeder Substrate Engineering

Chien

Lin

Huang

et al. 2022

Adv Healthcare Materials

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The intricate functionalities of cellular membranes have inspired strategies for deriving and anchoring cell‐surface components onto solid substrates for biological studies, biosensor applications, and tissue engineering. However, introducing conformal and right‐side‐out cell membrane coverage onto planar substrates requires cumbersome protocols susceptible to significant device‐to‐device variability. Here, a facile approach for biomembrane functionalization of planar substrates is demonstrated by subjecting confluent cellular monolayer to intracellular hydrogel polymerization. The resulting cell–gel hybrid, herein termed GELL (gelated cell), exhibits extraordinary stability and retains the structural integrity, membrane fluidity, membrane protein mobility, and topology of living cells. In assessing the utility of GELL layers as a tissue engineering feeder substrate for stem cell maintenance, GELL feeder prepared from primary mouse embryonic fibroblasts not only preserves the stemness of murine stem cells but also exhibits advantages over live feeder cells owing to the GELL's inanimate, non‐metabolizing nature. The preparation of a xeno‐free feeder substrate devoid of non‐human components is further shown with HeLa cells, and the resulting HeLa GELL feeder effectively sustains the growth and stemness of both murine and human induced pluripotent stem cells. The study highlights a novel bio‐functionalization strategy that introduces new opportunities for tissue engineering and other biomedical applications.

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Using high throughput screens to predict miscarriages with placental stem cells and long‐term stress effects with embryonic stem cells

Puscheck

Ruden

Singh

et al. 2022

Birth Defects Research

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A problem in developmental toxicology is the massive loss of life from fertilization through gastrulation, and the surprising lack of knowledge of causes of miscarriage. Half to two‐thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures. At the lower 50% estimate, miscarriage causes greater loss‐of‐life than all cancers combined or of all cardio‐ and cerebral‐vascular accidents combined. Surprisingly, we do not know if miscarriage rates are increasing or decreasing. Overshadowed by the magnitude of miscarriages, are insufficient data on teratogenic or epigenetic imbalances in surviving embryos and their stem cells. Superimposed on the difficult normal trajectory for peri‐gastrulation embryos are added malnutrition, hormonal, and environmental stresses. An overarching hypothesis is that high throughput screens (HTS) using cultured viable reporter embryonic and placental stem cells (e.g., embryonic stem cells [ESC] and trophoblast stem cells [TSC] that report status using fluorescent reporters in living cells) from the pre‐gastrulation embryo will most rapidly test a range of hormonal, environmental, nutritional, drug, and diet supplement stresses that decrease stem cell proliferation and imbalance stemness/differentiation. A second hypothesis is that TSC respond with greater sensitivity in magnitude to stress that would cause miscarriage, but ESC are stress‐resistant to irreversible stemness loss and are best used to predict long‐term health defects. DevTox testing needs more ESC and TSC HTS to model environmental stresses leading to miscarriage or teratogenesis and more research on epidemiology of stress and miscarriage. This endeavor also requires a shift in emphasis on pre‐ and early gastrulation events during the difficult period of maximum loss by miscarriage.

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Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines

Cited by 36 publications

References 12 publications

Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

In Situ Hydrogelation of Cellular Monolayers Enables Conformal Biomembrane Functionalization for Xeno‐Free Feeder Substrate Engineering

Using high throughput screens to predict miscarriages with placental stem cells and long‐term stress effects with embryonic stem cells

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