Somatic and germ cell parasitism in a colonial ascidian: Possible role for a highly polymorphic allorecognition system

Stoner, Douglas S.; Weissman, Irving L.

doi:10.1073/pnas.93.26.15254

Cited by 154 publications

(113 citation statements)

References 28 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…When DNA sequence allelic markers could be developed, we found that itinerant somatic and germline stem cells could move from colony zooid to other colony zooid, could participate in organogenesis, and later in the growing season could invade the incipient ovary and testis forming in every individual in the colony (181,182). Amazingly, Doug Stoner, Buki Rinkevich, and I showed that there were competitions between stem cell clones, the most dramatic at the level of formation of the germline stem cells, as measured by allelic polymorphisms shown in sperm and eggs (181,182).…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

“…Amazingly, Doug Stoner, Buki Rinkevich, and I showed that there were competitions between stem cell clones, the most dramatic at the level of formation of the germline stem cells, as measured by allelic polymorphisms shown in sperm and eggs (181,182). There could be tens of genotype A colony individuals naturally parabiosed with tens of colony B, but in all reproductive organs we found that only colony A would be the next generation's germline (181,182). This winner-loser outcome was independent of colony size and was heritable on repeats in both asexual and sexual reproductive inheritance (181).…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

See 1 more Smart Citation

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

View full text Add to dashboard Cite

I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

show abstract

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

View full text Add to dashboard Cite

show abstract

“…Although they must share at least one allele at this locus, they may be genetically different, and thus exploitation can occur (Stoner & Weissman, 1996). This can occur either by one clone totally dominating the other, often because it was older (Rinkevich et al, 1993), or by one invading the germ line of the other (Stoner & Weissman, 1996).…”

Section: Dominance Hierarchies In Other Systemsmentioning

confidence: 99%

A linear dominance hierarchy among clones in chimeras of the social amoeba Dictyostelium discoideum

Fortunato

Queller

Strassmann

2003

Journal of Evolutionary Biology

102

View full text Add to dashboard Cite

Amoebae from different clones of Dictyostelium discoideum aggregate into a common slug, which migrates towards light for dispersal, then forms a fruiting body consisting of a somatic, dead stalk, holding up a head of living spores. Contributions of two clones in a chimera to spore and stalk are often unequal, with one clone taking advantage of the other's stalk contribution. To determine whether there was a hierarchy of exploitation among clones, we competed all possible pairs among seven clones and measured their relative representation in the prespore and prestalk stages and in the final spore stage. We found a clear linear hierarchy at the final spore stage, but not at earlier stages. These results suggest that there is either a single principal mechanism or additive effects for differential contribution to the spore, and that it involves more than spore/stalk competition.

show abstract

“…Lastly, one puzzling phenomenon in these studies is that, whereas fused partners rarely maintain stability at the level of the colony, the eliminated partner may still persist, but at the level of the cell lineage (8,9). Those cells that escape allogeneic resorption may even parasitize the nonresorbed partner.…”

Section: Significancementioning

confidence: 99%

“…One chimeric partner is often eliminated in a process of allogeneic resorption, suggesting a break in immunological nonreactivity. Moreover, the eliminated partner may still persist, and even parasitize the nonresorbed partner, but at the level of the cell lineage (8,9). Insight has been gained into fusion-partner resorption from observational studies showing physical similarities with the developmental period known as "takeover," or blastogenic stage D (4, 10).…”

mentioning

confidence: 99%

Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners

Corey

Rosental

Kowarsky

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In a primitive chordate model of natural chimerism, one chimeric partner is often eliminated in a process of allogeneic resorption. Here, we identify the cellular framework underlying loss of tolerance to one partner within a natural Botryllus schlosseri chimera. We show that the principal cell type mediating chimeric partner elimination is a cytotoxic morula cell (MC). Proinflammatory, developmental cell death programs render MCs cytotoxic and, in collaboration with activated phagocytes, eliminate chimeric partners during the "takeover" phase of blastogenic development. Among these genes, the proinflammatory cytokine IL-17 enhances cytotoxicity in allorecognition assays. Cellular transfer of FACS-purified MCs from allogeneic donors into recipients shows that the resorption response can be adoptively acquired. Transfer of 1 × 10 5 allogeneic MCs eliminated 33 of 78 (42%) recipient primary buds and 20 of 76 (20.5%) adult parental adult organisms (zooids) by 14 d whereas transfer of allogeneic cell populations lacking MCs had only minimal effects on recipient colonies. Furthermore, reactivity of transferred cells coincided with the onset of developmental-regulated cell death programs and disproportionately affected developing tissues within a chimera. Among chimeric partner "losers," severe developmental defects were observed in asexually propagating tissues, reflecting a pathologic switch in gene expression in developmental programs. These studies provide evidence that elimination of one partner in a chimera is an immune cell-based rejection that operates within histocompatible pairs and that maximal allogeneic responses involve the coordination of both phagocytic programs and the "arming" of cytotoxic cells.T he colonial marine species, Botryllus schlosseri, offers a unique platform to study mechanisms underlying loss of tolerance in a natural model system. Colonies undergo a genetically controlled histocompatibility reaction that can result in vascular fusion of distinct genotypes, creating a chimera (1, 2). Natural history studies among fused colonies show that partners rarely exist as stable chimeras (3-7). One chimeric partner is often eliminated in a process of allogeneic resorption, suggesting a break in immunological nonreactivity. Moreover, the eliminated partner may still persist, and even parasitize the nonresorbed partner, but at the level of the cell lineage (8, 9). Insight has been gained into fusion-partner resorption from observational studies showing physical similarities with the developmental period known as "takeover," or blastogenic stage D (4, 10). B. schlosseri colonies are composed of clonogenic individuals, termed "zooids," that undergo weekly cycles of death and regeneration, culminating in a massive wave of programmed cell death and removal, or takeover (11). These studies support the involvement of activated phagocytes in the elimination of tissues of the "losing" partner.Here, we study the progression by which fused colonies eliminate chimeric partners and show that partner eliminatio...

show abstract

Somatic and germ cell parasitism in a colonial ascidian: Possible role for a highly polymorphic allorecognition system

Cited by 154 publications

References 28 publications

How One Thing Led to Another

How One Thing Led to Another

A linear dominance hierarchy among clones in chimeras of the social amoeba Dictyostelium discoideum

Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners

Contact Info

Product

Resources

About