Single-Cell RNA Sequencing of Human Pluripotent Stem Cell-Derived Macrophages for Quality Control of The Cell Therapy Product

Hye-Yeong Jo; Hyang-Hee Seo; Dayeon Gil; YoungChan Park; Hyeong-Jun Han; Hyo-Won Han; Rajesh K Thimmulappa; Sang Cheol Kim; Jung-Hyun Kim

doi:10.3389/fgene.2021.658862

Single-Cell RNA Sequencing of Human Pluripotent Stem Cell-Derived Macrophages for Quality Control of The Cell Therapy Product

Front Genet. 2022 Jan 31:12:658862. doi: 10.3389/fgene.2021.658862. eCollection 2021.

Authors

Hye-Yeong Jo^{1

2

3}, Hyang-Hee Seo^{1

2}, Dayeon Gil^{1

2}, YoungChan Park⁴, Hyeong-Jun Han^{1

2}, Hyo-Won Han^{1

2}, Rajesh K Thimmulappa⁵, Sang Cheol Kim³, Jung-Hyun Kim^{1

2}

Affiliations

¹ Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, South Korea.
² Korea National Stem Cell Bank, Cheongju, South Korea.
³ Division of Healthcare and AI, Center for Precision Medicine, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, South Korea.
⁴ Oneomics, Bucheon-si, South Korea.
⁵ Department of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, India.

Abstract

Macrophages exhibit high plasticity to achieve their roles in maintaining tissue homeostasis, innate immunity, tissue repair and regeneration. Therefore, macrophages are being evaluated for cell-based therapeutics against inflammatory disorders and cancer. To overcome the limitation related to expansion of primary macrophages and cell numbers, human pluripotent stem cell (hPSC)-derived macrophages are considered as an alternative source of primary macrophages for clinical application. However, the quality of hPSC-derived macrophages with respect to the biological homogeneity remains still unclear. We previously reported a technique to produce hPSC-derived macrophages referred to as iMACs, which is amenable for scale-up. In this study, we have evaluated the biological homogeneity of the iMACs using a transcriptome dataset of 6,230 iMACs obtained by single-cell RNA sequencing. The dataset provides a valuable genomic profile for understanding the molecular characteristics of hPSC-derived macrophage cells and provide a measurement of transcriptomic homogeneity. Our study highlights the usefulness of single cell RNA-seq data in quality control of the cell-based therapy products.

Keywords: Pluripotent stem cell; cell therapy product; macrophage; quality control; single-cell RNA sequencing.