A conserved germline multipotency program

Abstract

The germline of multicellular animals is segregated from somatic tissues, which is an essential developmental process for the next generation. Although certain ecdysozoans and chordates segregate their germline during embryogenesis, animals from other taxa segregate their germline after embryogenesis from multipotent progenitor cells. An overlapping set of genes, including vasa, nanos and piwi, operate in both multipotent precursors and in the germline. As we propose here, this conservation implies the existence of an underlying germline multipotency program in these cell types that has a previously underappreciated and conserved function in maintaining multipotency.Key words: Germline, Stem cell, Vasa, Piwi, Nanos, Sea urchin Introduction Multicellular animals consist of specialized cells, most of which are differentiated and devoid of reproductive potential. However, some cells, such as stem cells, retain both the ability to self-renew and to create new differentiated cells. One such stem cell, the germline stem cell (GSC), gives rise to a continual supply of germ cells, which are specialized for the task of reproduction. Yet once egg and sperm fuse, the resulting zygote is totipotent, and thus can give rise to all cell types of the animal. Although GSCs normally give rise only to germ cells in vivo, and thus are unipotent, a significant body of evidence shows that these cells maintain the potential to acquire many cell fates. For example, mouse primordial germ cells (PGCs) acquire the morphological and cytological characteristics of embryonic stem (ES) cells when cultured in the presence of three growth factors: steel factor, leukemia inhibitory factor (LIF) and fibroblast growth factor (FGF) (Matsui et al., 1992). These cells create teratomas when injected into adult mice and chimeric pups when injected into blastocysts, thus demonstrating their pluripotency. Isolated human PGCs can also be converted to pluripotent stem cells without genetic manipulation (Shamblott et al., 1998). Furthermore, pluripotent cells spontaneously arise from isolated adult mouse spermatogonial stem cells under specific culture conditions (Guan et al., 2006). This phenomenon is not limited to vertebrates as mutations in the translational regulators mex-3 and gld-1 in Caenorhabditis elegans leads to transdifferentiation of germ cells into muscle, neurons and intestinal cells (Ciosk et al., 2006). Thus, although germ cells are highly specialized, they seemingly retain the capacity to give rise to all cell types. As such, it is possible that the developmental potential of GSCs in these organisms is not intrinsically limited but might instead be restricted by environment. What, then, is the underlying regulatory program that controls this highly potent cell type?The molecular regulation of the germline is best understood in a handful of animals, including in C. elegans, Drosophila melanogaster and the mouse. Here, we explore the diversity of germline origins more broadly by examining germline segregation mechanisms across diverse taxa f...

Characterization of the piRNA pathway during development of the sea anemone Nematostella vectensis

“…9,10 Therefore, these piRNA pathway components have been suggested to be part of an ancestral gene repertoire conserved from sponges to vertebrates responsible for maintenance of "stemness" in germline stem cells as well as somatic stem cells, referred to as germline mulitpotency program (GMP). 11,12 The phylum Cnidaria, which includes corals, sea anemones, jellyfish and hydroids, is the sister group to Bilateria 13 and thus provides a unique opportunity to study the evolution of shared mechanisms and pathways. Recently, piRNAs and PIWI proteins were identified in the cnidarian Hydra.…”

Germline development in amniotes: A paradigm shift in primordial germ cell specification

“…In the animal kingdom, vertebrates and ecdysozoans (such as C. elegans and Drosophila ) are thought to adopt an early soma‐germ line segregation, while other taxa maintain a multipotent population of cells which will give rise to germ cells in the adults 107, 108. We propose that even when the early segregation occurs, multipotent progenitors (presumably pPGCs) are established in the embryo, regardless of the defined modality of PGC formation adopted by the species.…”

“…The revision of data available on PGC specification in amniotes sheds doubts on the current tendency to divide embryos in two clear‐cut categories, the ones adopting maternal specification (predetermination) versus the ones employing induction (epigenesis), as previously suggested from studies focussing on non‐amniotes 3, 107, 108. The only amniote species where the molecular mechanism of induction has been dissected is the mouse.…”

“…We propose that even when the early segregation occurs, multipotent progenitors (presumably pPGCs) are established in the embryo, regardless of the defined modality of PGC formation adopted by the species. These multipotent precursors can give rise to the germ line either during embryonic development or adult life 3, 107, 108. The question remains as to when and by which mechanism those pPGCs are established (retention of maternal transcripts, germ plasm, induction etc).…”

Amphioxus regeneration: evolutionary and biomedical implications

“…Reports in a number of animals suggest that the germ-soma divide is not strict, and that mechanisms used to maintain the PGCs/ germline may also be utilised in somatic stem cells, supporting the existence of an ancestral multipotency programme already in the last common ancestor of metazoans (Juliano et al, 2010;FierroConstain et al, 2017). Thus, many "germline"-associated genes are also expressed in pluripotent somatic progenitors, and can be re-activated during regenerative processes.…”