Evolutionary Origin of the Mammalian Hematopoietic System Found in a Colonial Chordate

Abstract

SummaryHematopoiesis 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. Using flow-cytometry, whole-transcriptome sequencing of defined cell populations, and diverse functional assays, we identified HSCs, progenitors, immuneeffector cells, the HSC niche, and demonstrated that self-recognition inhibits cytotoxic reaction. 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.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/206318 doi: bioRxiv preprint first posted online Dec. 26, 2017; 3 Hematopoietic stem cells (HSCs) are multipotent, self-renewing cells that generate all mature blood and immune cell populations throughout life. In mammals, the blood-forming organ is the bone marrow, where HSCs reside in specialized niches that support their self-renewal and maintenance of an undifferentiated state. Since the identification of HSCs by prospective isolation 1 , several model systems have been studied to elucidate HSC biology [2][3][4][5][6][7][8] . While there are comprehensive studies on vertebrate HSC self-renewal, differentiation, physiological regulation and niche occupation, relatively little is known about their evolutionary origin and niches. To gain insight into the evolutionary origin of the mammalian hematopoietic and immune system, and identify fundamental cell and molecular mechanisms underlying HSCs homeostasis and regeneration we characterized the blood and immune system of the colonial tunicate Botryllus schlosseri.Tunicates are marine invertebrates in the phylum Chordata that share the chordate characteristics of a notochord, dorsal neural tube, and gill slits in their free-swimming larval stage, but lose most of these features during metamorphosis into sessile adults 9,10 . In B. schlosseri, after metamorphosis, a colony is formed via asexual reproduction consisting of multiple individuals, called zooids, through a stem-cell-mediated budding process that continues throughout life 11. Every week, the developed buds replace the parent zooids that undergo synchronized programmed cell death 12 (Movie S1). Each mature zooid has digestive and respiratory systems, a tub...