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

Abstract

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.

Noninvasive analysis of contractility during identical maturations revealed two phenotypes in ventricular but not in atrial iPSC-CM

“…Furthermore, sex differences related to X-chromosome dosage were described only to influence the differentiation ratio of iPSC toward cardiomyocytes and epicardium-derived cells ( 49 ) whereas, in the present study, we focused on the fate of differentiated iPSC-CMs only. We recognize the current sex inequality in stem cell research as stated ( 48 ) but feel that gender differences will not influence qualitatively the interpretation of our results.…”

“…Another limitation of our study is that we used only one iPSC line from a male donor. However, although differential gene expression was recently reported in male and female iPSC-CMs ( 48 ), the identified genes were not related to genes involved in cardiac contractility. Furthermore, sex differences related to X-chromosome dosage were described only to influence the differentiation ratio of iPSC toward cardiomyocytes and epicardium-derived cells ( 49 ) whereas, in the present study, we focused on the fate of differentiated iPSC-CMs only.…”

An efficient induction method for human spinal lower motor neurons and high-throughput image analysis at the single cell level

“…Because ALS symptoms progress rapidly and daily physical activities become impossible for patients within 1-2 years, rapid establishment of patient-derived iPSCs and drug screening of MNs are essential for precision medicine. Although there are many problems to be solved in the practical application of personalized medicine using iPS cells (Shin et al, 2018, Novelli et al, 2023, Palasantzas et al, 2023, Nguyen et al, 2023, we believe that our method can shorten the time required for drug screening and contribute to practical application.…”