Is the Germline Immortal and Continuous? A Discussion in Light of iPSCs and Germline Regeneration

The germline gives rise to gametes, is the hereditary cell lineage, and is often called immortal and continuous. However, what exactly is immortal and continuous about the germline has recently come under scrutiny. The notion of an immortal and continuous germline has been around for over 130 years, and has led to the concept of a barrier between the germline and soma (the “Weismann barrier”). One repercussion of such a barrier is the understanding that when the germline is lost, soma cannot replace it, rendering the organism infertile. Recent research on induced pluripotent stem cells (iPSCs) and germline regeneration raise questions about the impermeability of the Weismann barrier and the designation of the germline as immortal and continuous. How we conceive of the germline and its immortality shapes what we perceive to be possible in animal biology, such as whether somatic cells contribute to the germline in some metazoans during normal development or regeneration. We argue that reassessing the universality of germline immortality and continuity across all metazoans leads to big and exciting open questions about the germ-soma cell distinction, cell reprogramming, germline editing, and even evolution.