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Urochordata: Botryllus – Natural Chimerism and Tolerance Induction in a Colonial Chordate

  • Ayelet Voskoboynik
  • Aaron M. Newman
  • Mark Kowarsky
  • Irving L. Weissman
Chapter

Abstract

Chimerism is defined as the coexistence of two or more genomes of separate origin within an individual. In placental mammals such as humans, natural chimerism develops during pregnancy between a mother and fetus and has an important role in the induction of fetal tolerance to maternal tissues. Natural chimerism between kin also occurs in colonial ascidians, the closest extant ancestors of chordates. In the ascidian, Botryllus schlosseri, some colonies fuse to create lifelong chimeric entities of two allogeneic genomes. The decision to fuse in B. schlosseri is governed by a polymorphic histocompatibility gene called the Botryllus histocompatibility factor (BHF). Colonies that share at least one BHF allele fuse upon contact, whereas colonies without any BHF alleles in common ultimately reject. Following vasculature fusion, stem cells from each histocompatible B. schlosseri colony compete to overtake germline or somatic lineages. Stem cell competition may lead to elimination of the other colony’s genome, or it may produce a chimeric colony with mixed genotypes. In this way, chimerism in B. schlosseri represents a nexus between stem cell competition, genome parasitism, and allorecognition. Here we review studies conducted over six decades that led to the discoveries of the nature of the cells that mediate chimerism in colonial ascidians and the gene that controls it.

Keywords

Parabiont Chimerism Microchimerism Stem cell competition Histocompatibility Immunologic tolerance BHF Tunicate Ascidian Botryllus schlosseri 

Notes

Acknowledgments

In memory of Professor Yasunori Saito, who established the homozygous and heterozygous B. schlosseri lines for distinct fusibility histocompatibility alleles. We thank Katherine Ishizuka and Karla Palmeri for raising, crossing, and maintaining these lines and an intensive Botryllus frozen sample collection in our lab for three decades. This study was supported by National Institutes of Health Grants 1R01AG037968 and R01GM100315 awarded to I.L.W. and A.V. and the Virginia and D. K. Ludwig Fund for Cancer Research awarded to I.L.W.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ayelet Voskoboynik
    • 1
    • 2
  • Aaron M. Newman
    • 1
  • Mark Kowarsky
    • 3
  • Irving L. Weissman
    • 1
    • 2
    • 4
  1. 1.Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of MedicineStanfordUSA
  2. 2.Hopkins Marine Station, Stanford UniversityPacific GroveUSA
  3. 3.Department of PhysicsStanford UniversityStanfordUSA
  4. 4.Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of MedicineStanfordUSA

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