Single cell transcriptomes of zebrafish germline reveal progenitor types and feminization by Foxl2l

Abstract
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Abstract

Zebrafish is an important organism for genetic studies, but its early germ cell types and the mechanism of sex differentiation have not been fully characterized. Here, we profiled single-cell transcriptomes and charted a developmental trajectory going from germline stem cells, through early, committed, and late progenitors, to pre-meiotic and meiotic cells. We showed that transcription factor Foxl2l expressed in the progenitor directed progenitor differentiation toward oocytes. CRISPR-Cas9-mediated mutation of foxl2l produced 100% male fish with normal fertility. Another single-cell profiling of foxl2l^-/- germ cells revealed the arrest of germ cell development at the stage of progenitor commitment. Concomitantly, nanos2 transcript (germline stem cell marker) was elevated together with an increase of nanos2⁺ germ cells in foxl2l mutants, indicating the acquisition of a novel stem cell state. Thus, we have identified developmental stages of germ cells in juvenile zebrafish and demonstrated that zebrafish Foxl2l drives progenitor germ cells toward feminization and prevents them from expressing nanos2.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE173718.

The following data sets were generated

1. BC Chung
2. et al
(2025) Single cell transcriptomes of zebrafish germline reveal progenitor types and feminization by Foxl2l
NCBI Gene Expression Omnibus, GSE173718.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173718

The following previously published data sets were used

1. Liu Y et al
(2021) Single-cell transcriptome reveals insights into the development and function of the zebrafish ovary
NCBI Gene Expression Omnibus, GSE191137.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE191137

Article and author information

Author details

Chen-wei Hsu

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Ho Hao

Statistics Department, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8911-7907
Ching-Hsin Yang

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Yan-wei Wang

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Ker-Chau Li

Statistics Department, University of California, Los Angeles, Los Angeles, United States

For correspondence
kcli@math.ucla.edu

Competing interests
The authors declare that no competing interests exist.
Bon-Chu Chung

Neuroscience and Brain Disease Center, China Medical University, Taipei, Taiwan

For correspondence
mbchung@gate.sinica.edu.tw

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8612-0219

Funding

National Health Research Institutes (NHRI- EX107-10506SI)

Bon-Chu Chung

National Science and Technology Council (MOST 108-2311-B-001 -038 -MY3)

Bon-Chu Chung

National Science and Technology Council (NSTC 113-2313-B-492-001 -)

Bon-Chu Chung

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Zebrafish were handled under the guidelines of Institutional Animal Care and Utilization Committee of Academia Sinica and National Laboratory Animal Center of National Applied Research Laboratories (IACUC: 10-10-084, and NLAC-113-M-004-R1).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.