Germline stem and progenitor cells (GSPCs), including primordial germ cells (PGCs) and germline stem cells (GSCs), generate various states of germ stem cells and then differentiate into specialized cells, while self-renew to generate more stem cells. The formation, maintenance, and differentiation of GSPCs is essential for the animal reproduction process and it is regulated by a multitude of mechanisms. 

In addition to their long-recognized role in energy production, mitochondria may also regulate cell fate determination. The balance of mitochondrial fusion and fission, namely mitochondrial dynamics, is tightly related to cellular physiology and even cell fate. However, it remains unknown whether and how mitochondrial dynamics participates in GSPCs development and gonadal differentiation. 

Recently, in collaboration with Prof. CHEN Zhenxia from Huazhong Agricultural University, a research group led by Prof. SUN Yonghua from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences demonstrated the novel mechanisms that germline-specific mitochondrial organization is necessary for the maintenance and differentiation of GSPCs. This study was published as back cover paper on Advanced Science.  

In this study, by cross-analyzing the RNA sequencing results of zebrafish juvenile testes and ovaries, researchers found that the mitochondrial organization process was significantly enriched by Gene Ontology analysis and identified mitoPLD (zebrafish pld6) as a novel germline-specific gene related to mitochondrial fusion.  

By generating pld6-knockout mutants, the researchers found that zygotic disruption of pld6 did not affect the initial number of GSPCs, whereas the mutants had a small size in gonads at 25 dpf and the GSPCs failed to differentiate into early oocytes thereafter. The germ cells disappeared in the mutants after 35 dpf, eventually leading to masculinization and infertility of the mutants. Mitochondrial fusion in the pld6-depleted GSPCs was severely impaired either. 

These findings firstly uncover zebrafish Pld6 as a novel germline-specific regulator of mitochondrial fusion, and highlights its essential role in the maintenance and differentiation of GSPCs as well as in gonadal development and gametogenesis.  

Emperor Yu Tames the Flood (Image by IHB)
The cover adopts the concept of ancient Chinese myth and legend "Emperor Yu Tames the Flood". Yellow River, the "mother river of China" represents the germline which is the vehicle of reproduction. The artifact leisi handheld by Dayu represents the mitochondrial fusion factor in germline-Pld6. Emperor Yu governances mitochondrial fusion by Pld6 in the germline (Yellow River), thus ensuring the balance of self-renewal and differentiation of GSPCs. 

(Editor: MA Yun)