Evolutionary Foundation of the Mammalian Hematopoietic Stem Cells and Immune Systems Found in a Colonial Chordate.

Hematopoiesis is an essential process that evolved in multicellular animals. At the heart of this process are hematopoietic stem cells (HSCs), which are multipotent, self-renewing and generate the entire repertoire of blood and immune cells throughout life. Here we studied the hematopoietic system of Botryllus schlosseri, a colonial tunicate that has vasculature, circulating blood cells, and interesting characteristics of stem cell biology and immunity. Self-recognition between genetically compatible B. schlosseri colonies leads to the formation of natural parabionts with shared circulation, whereas incompatible colonies reject each other. By means of flow-cytometry in combination with screened antibodies by Cytof, lectins, and fluorescent enzymatic reagents, we isolated 34 B. schlosseri cell populations. Using whole-transcriptome sequencing of defined cell populations, and diverse functional assays, we identified HSCs, progenitors, immune-effector cells, and the HSC niche. Our study implies that the HSC and myeloid lineages emerged in a common ancestor of tunicates and vertebrates and suggests that hematopoietic bone marrow and the B. schlosseri endostyle niche evolved from the same origin. Furthermore, we identified a B. schlosseri cytotoxic cell population originating from large granular lymphocyte-like cells and demonstrated that self-recognition inhibits cytotoxic reaction.

References: Corey DM* and Rosental B* et al. Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners. PNAS, 2016.

Rosental B, and Kowarsky et al. Complex mammalian-like haematopoietic system found in a colonial chordate. Nature, 2018.