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Divergent Roles of KLF4 During Primordial Germ Cell Fate Induction from Human Embryonic Stem Cells

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Abstract

As a core transcriptional factor regulating pluripotency, Krüppel-like factor 4 (KLF4) has gained much attention in the field of stem cells during the past decades. However, few research have focused on the function of KLF4 during human primordial germ cell (PGC) specification. Here, we induced human PGC-like cells (hPGCLCs) from human embryonic stem cells (hESCs) and the derived hPGCLCs upregulated PGC-related genes, like SOX17, BLIMP1, TFAP2C, NANOS3, and the naïve pluripotency gene KLF4. The KLF4-knockout hESCs formed typical multicellular colonies with clear borders, expressed pluripotency genes, such as NANOG, OCT4, and SOX2, and exhibited no differences in proliferation capacity compared with wild type hESCs. Notably, KLF4 deletion in hESCs did not influence the induction of PGCLCs in vitro. In contrast, overexpression of KLF4 during PGC induction process inhibited the efficiency of PGCLC formation from hESCs in vitro. Overexpression of KLF4 may regenerate the naïve ground state in hESCs and results in repression for PGC specification. Thus, KLF4 could be a downstream target of human PGC program and the upregulation of KLF4 is prepared for late stage of germline development.

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Data Availability

The data is available on request from the authors.

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Funding

This work was financially supported by grants from the National Natural Science Foundation of China to Fang Fang (no. 81901484).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China

    Fang Fang & Shi Lu

  2. Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Zili Li

  3. Department of Reproductive Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Xiaoke Zhang

  4. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Qi Huang

  5. Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Xiao Wang

Authors
  1. Fang Fang
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  2. Zili Li
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  3. Xiaoke Zhang
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  4. Qi Huang
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  5. Shi Lu
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  6. Xiao Wang
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Contributions

The study was conceived and designed by FF and XW. FF and ZL conducted the experiments and analyzed the data. FF and XZ wrote the manuscript with the help from QH and SL. The study was supervised by XW and SL. The final vision was approved by all authors.

Corresponding authors

Correspondence to Shi Lu or Xiao Wang.

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Ethics Approval

The Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (IORG No: IORG0003571) gave final approval for the study on the function of Krüppel-like factor 4 and related mechanism in the regulation network of human primordial germ cell specification which is conducted by Dr. Fang Fang at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

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The manuscript has been approved for publication by all the authors.

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Fang, F., Li, Z., Zhang, X. et al. Divergent Roles of KLF4 During Primordial Germ Cell Fate Induction from Human Embryonic Stem Cells. Reprod. Sci. 31, 727–735 (2024). https://doi.org/10.1007/s43032-023-01360-3

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  • DOI: https://doi.org/10.1007/s43032-023-01360-3

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