Conversion of Germ Cells to Somatic Cell Types in C. elegans.

Nida Ul Fatima,Baris Tursun

doi:10.3390/jdb8040024

Abstract

The potential of a cell to produce all types of differentiated cells in an organism is termed totipotency. Totipotency is an essential property of germ cells, which constitute the germline and pass on the parental genetic material to the progeny. The potential of germ cells to give rise to a whole organism has been the subject of intense research for decades and remains important in order to better understand the molecular mechanisms underlying totipotency. A better understanding of the principles of totipotency in germ cells could also help to generate this potential in somatic cell lineages. Strategies such as transcription factor-mediated reprogramming of differentiated cells to stem cell-like states could benefit from this knowledge. Ensuring pluripotency or even totipotency of reprogrammed stem cells are critical improvements for future regenerative medicine applications. The C. elegans germline provides a unique possibility to study molecular mechanisms that maintain totipotency and the germ cell fate with its unique property of giving rise to meiotic cells Studies that focused on these aspects led to the identification of prominent chromatin-repressing factors such as the C. elegans members of the Polycomb Repressive Complex 2 (PRC2). In this review, we summarize different factors that were recently identified, which use molecular mechanisms such as control of protein translation or chromatin repression to ensure maintenance of totipotency and the germline fate. Additionally, we focus on recently identified factors involved in preventing transcription-factor-mediated conversion of germ cells to somatic lineages. These so-called reprogramming barriers have been shown in some instances to be conserved with regard to their function as a cell fate safeguarding factor in mammals. Overall, continued studies assessing the different aspects of molecular pathways involved in maintaining the germ cell fate in C. elegans may provide more insight into cell fate safeguarding mechanisms also in other species.

Highlights

The potential of a cell to produce all types of differentiated cells in an organism is termed totipotency
Strategies such as transcription factor-mediated reprogramming of differentiated cells to stem cell-like states could benefit from this knowledge
The C. elegans germline provides a unique possibility to study molecular mechanisms that maintain totipotency and the germ cell fate with its unique property of giving rise to meiotic cells Studies that focused on these aspects led to the identification of prominent chromatin-repressing factors such as the C. elegans members of the Polycomb Repressive Complex 2 (PRC2)

Summary

Translational Regulators Maintain Germline Totipotency and Prevent Teratomas

In the absence of these mechanisms, germ cells can differentiate to somatic cells thereby forming germline teratomas with co-occurrence of multiple somatic lineages at once Such teratomas form upon loss of the translational regulators GLD-1 (ortholog of human KH-domain containing RNA-binding protein QKI) and MEX-3. (ortholog of human MEX3A RNA-binding protein) and germ cells acquire somatic fates including muscle, neuron and intestine [1] These teratomas arise spontaneously in most of the gld-1 mex-3 double mutants, and in gld-1 mutant alone to a lesser extent. Expression of transcription factors such as PAL-1 and HLH-1 in combination with affected maintenance of the germ cell fate may allow conversions to somatic cell types These defects could include loss of P granules as observed in the gld-1 mex-3 mutants and defective chromatin regulation, which altogether lead to teratoma formation in the germline

P Granules Safeguard Germline Identity

Transcription

LIN-53 Cooperates with PRC2 to Prevent Permits Germ Cell Reprogramming by TFs

LIN-53 and PRC2 Antagonize Notch Signaling-Enhanced Germ Cell Reprogramming

Outlook