Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming

Yuling Peng; Jieying Zhu; Qi Zhang; Ran Zhang; Zhenhua Wang; Zesen Ye; Ning Ma; Dajiang Qin; Duanqing Pei; Dongwei Li

doi:10.1186/s13619-024-00200-2

Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming

Cell Regen. 2024 Sep 13;13(1):17. doi: 10.1186/s13619-024-00200-2.

Authors

Yuling Peng^#^{1

2}, Jieying Zhu^#³, Qi Zhang^#^{1

2}, Ran Zhang⁴, Zhenhua Wang¹, Zesen Ye⁵, Ning Ma⁵, Dajiang Qin^{1

2

3

6

7}, Duanqing Pei⁸, Dongwei Li⁹

Affiliations

¹ Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, China.
² Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China.
³ CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Institutes of Biomedicine and Health, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Hong Kong Institute of Science & Innovation, Guangzhou, Guangzhou, Guangdong, 510530, China.
⁴ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
⁵ Guangzhou National Laboratory, Guangzhou, China.
⁶ GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
⁷ Guangdong Engineering Research Center of Early Clinical Trials of Biotechnology Drugs, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
⁸ Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, 310024, China.
⁹ Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, China. lidongwei@gzhmu.edu.cn.

^# Contributed equally.

Abstract

Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming.

Keywords: ERVH48-1; Endogenous retroviruses; Human embryonic stem cells; Induced pluripotent stem cells; Urine cell integration-free reprogramming system.