The skeletal harboring of hematopoietic stem cells (HSCs) is generally considered as vertebrate-specific innovation during water-to-land transition. However, this long-standing view has not been rigorously evaluated as hematopoietic sites remain poorly understood in most invertebrate groups. Herein, we report the first discovery of abundant HSCs in adult mollusk shells, an invertebrate hematopoietic niche that resembles vertebrate bone marrow (BM). Bulk and single-cell transcriptome profiling showed that mollusk shells are composed of abundant HSC-like cells, which distinguish shells from adult soft tissues or organs and functionally resemble vertebrate BM-HSCs. Cell lineage analysis and functional assays revealed the developmental origin of HSCs during larval shell formation and their participation in hemocyte-mediated shell regeneration and soft body blood supply. Widespread skeleton-related HSC-like cells are found in diverse invertebrate groups. Contrary to the common view of vertebrate-specific innovation, our study reveals the widespread and potentially deep evolutionary origins of invertebrate skeletal HSC niches, thereby boosting new paradigms for hematopoiesis and stem cell research in invertebrates.
Widespread presence of bone marrow-like hematopoietic stem cell niche in invertebrate skeletons