Human-Induced Pluripotent Stem Cell–Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases

Kiris, Erkan

doi:10.1007/5584_2021_683

Cited by 5 publications

(2 citation statements)

References 319 publications

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“…The Wnt pathway is widely associated with cell fate during embryonic development which could explain the differing transcriptomes. In addition, it was found that sex plays a large biological role in the development of central nervous system disorders due to the differences in gene expression ( Kiris, 2022 ). This difference in transcriptome is also found in myeloid cells when iPSC were used as a model for Alzheimer’s ( Coales et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes

Nguyen

Lac

Abdi

et al. 2023

Front. Cell Dev. Biol.

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In vitro investigation on human development, disease modeling, and drug discovery has been empowered by human induced pluripotent stem cell (hiPSC) technologies that form the foundation of precision medicine. Race and sex genetic backgrounds have become a major focus of many diseases modeling and drug response evaluation in the pharmaceutical industry. Here, we gathered data from major stem cell repositories to analyze the diversity with respect to ethnicity, sex, and disease types; and we also analyzed public datasets to unravel transcriptomics differences between samples of different ethnicities and sexes. We found a lack of diversity despite the large sample size of human induced pluripotent stem cells. In the ethnic comparison, the White group made up the majority of the banked hiPSCs. Similarly, for the organ/disease type and sex comparisons, the neural and male hiPSCs accounted for the majority of currently available hiPSCs. Bulk RNA-seq and single-cell transcriptomic analysis coupled with Machine Learning and Network Analysis revealed panels of gene features differently expressed in healthy hiPSCs and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of different races and sexes. The data highlights the current ethnic and sex inequality in stem cell research and demonstrates the molecular biological diversity of hiPSCs and cardiomyocytes from different races and genders. We postulate that future efforts in stem cell biology, regenerative and precision medicine should be guided towards an inclusive, diverse repository reflecting the prevalence of diseases across racial and ethnic groups and the sexes, important for both common and rare disease modeling, drug screening, and cell therapeutics.

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Section: Discussionmentioning

confidence: 99%

Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes

Nguyen

Lac

Abdi

et al. 2023

Front. Cell Dev. Biol.

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“…29 Later, immortalised cells were added to the portfolio, with human embryonic stem cells and induced pluripotent stem cells also entering the arena. 30,31 Some advantages of cell lines include the possibility of storing frozen stocks and producing large numbers of cells with high uniformity, while primary cells represent the genetic diversity present within a given human population. Immortalisation and transfection techniques have been applied to primary cells to establish immortalised cell lines, but as a result, gene expression patterns may change considerably.…”

Section: Recent Funding Policy Changesmentioning

confidence: 99%

A Short History of the Consideration of Sex Differences in Biomedical Research — Lessons for the In Vitro Community from Animal Models and Human Clinical Trials

Gutleb

2023

Altern Lab Anim

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In recent decades, it has become clear that in many fields — such as drug development, particularly with regard to drug dosage and specific disease treatment — the sex of a patient must be taken into consideration, in view of the fact that male and female physiology and pathophysiology show many differences of practical concern. While, in the last decade or so, considerable efforts have been undertaken to consider the sex of the animals during the planning of experiments, this topic has just started to be acknowledged in in vitro studies. Cells in such studies seem mainly to be used according to their availability, without considering the sex of the original donor. Even when such information is available, experimental data are reported without overtly detailing this information. In recent years, the increasing complexity of in vitro models (e.g. stem cell-based, 3-D cultures, organoids, or organ-on-a-chip technologies) has contributed to systems that better resemble the human in vivo situation. However, the issue of the sex of the experimental organisms being used has not yet been properly taken up by the cell culture community. Thus, alongside the increasing complexity of multicell-type models, we now see in vitro models that incorporate cells from both male and female origin — this representing, in fact, a genetic chimaera. Here, we aim to discuss where we are currently, with respect to considering the sex of any animals or humans used in experiments, and we try to identify what is lacking in the cell culture field, in order to help facilitate change.

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Chemical toxicity by sex differences: a literature review of 2019–2023 studies

Rim

2024

Toxicol. Environ. Health Sci.

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Human-Induced Pluripotent Stem Cell–Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases

Cited by 5 publications

References 319 publications

Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes

Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes

A Short History of the Consideration of Sex Differences in Biomedical Research — Lessons for the In Vitro Community from Animal Models and Human Clinical Trials

Chemical toxicity by sex differences: a literature review of 2019–2023 studies

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