For the past 20 years I have studied the biology of the urochordate Botryllus schlosseri and contributed to its development as a model organism for the study of stem cell biology, immunology and evolution. As a postdoctoral fellow in Irv Weissman’s lab. at Stanford, I identified and isolated the first adult stem cell (Cell Stem Cell, 2008) and the first germline stem cell niche in B. schlosseri (Dev. Cell, 2013). I also discovered that B. schlosseri exhibits an alternative regeneration pathway whereby whole body regeneration occurs from the vasculature alone: a process in which a normal colony of individuals is regenerated through multiple generations of abnormal intermediate forms that gradually converge into an individual with normal physiology and morphology (FASEB J., 2007). Since 2010, I have been directing and conducting the B. schlosseri genome project, a project that has involved 19 scientists in bioinformatics and molecular and cell biology from Irv Weissman’s and Stephen Quake’s labs and several international laboratories. Using our novel method for high-throughput sequencing of repeat-rich genomes (called LRseq; acquired by Illumina), we sequenced and assembled the 580-Mbp of the B. schlosseri genome. The B. schlosseri genome revealed critical events underlying the early evolution of vertebrates, including the first known appearance of genes related to hematopoiesis, cardiac, optic and auditory development (Elife, 2013). Using this newly sequenced B. schlosseri genome, we looked carefully into a single polymorphic gene locus that governs fusion/rejection outcomes in B. schlosseri colonies. This locus, encodes multiple co-dominant alleles in natural populations, and progeny from crosses between histocompatible colonies are known to segregate in a manner consistent with a monogenetic trait. Using genetically defined lines, whole-transcriptome sequencing of 23 colonies, and a novel genomics approach, we identified BHF, the gene that encodes self and determines “graft” outcomes in this organism. Our genome-wide study revealed the first fusion-rejection system understood to the point where one can reliably predict, based on a single gene, the outcome of histocompatibility reactions. These findings establish an experimentally tractable platform for advancing the science of allorecognition (Science, 2013). Using the resources and tools we and others developed we continue our studies on BHF, the evolution of blood borne immune system and on stem cell mediated regeneration programs.
Voskoboynik, A., Newman, A. M., Corey, D. M., Sahoo, D., Pushkarev, D., Neff, N. F., … Weissman, I. L. (2013). Identification of a colonial chordate histocompatibility gene. Science , 341(6144), 384–387.
Voskoboynik, A., Neff, N. F., Sahoo, D., Newman, A. M., Pushkarev, D., Koh, W., … Quake, S. R. (2013). The genome sequence of the colonial chordate, Botryllus schlosseri. ELife, 2.
Voskoboynik, A., Soen, Y., Rinkevich, Y., Rosner, A., Ueno, H., Reshef, R., … Weissman, I. L. (2008). Identification of the Endostyle as a Stem Cell Niche in a Colonial Chordate. CELL STEM CELL, 3(4), 456–464.
Voskoboynik, A., Simon-Blecher, N., Soen, Y., Rinkevich, B., De Tomaso, A. W., Ishizuka, K. J., & Weissman, I. L. (2007). Striving for normality: whole body regeneration through a series of abnormal generations. FASEB JOURNAL, 21(7), 1335–1344.
Corey, D. M., rosental, B., Kowarsky, M., Sinha, R., Ishizuka, K. J., Palmeri, K. J., … Weissman, I. L. (2016). Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(23), 6520–25.
Gasparini, F., Skobo, T., Benato, F., Gioacchini, G., Voskoboynik, A., Carnevali, O., … Valle, L. D. (2016). Characterization of Ambra1 in asexual cycle of a non-vertebrate chordate, the colonial tunicate Botryllus schlosseri, and phylogenetic analysis of the protein group in Bilateria. MOLECULAR PHYLOGENETICS AND EVOLUTION, 95, 46–57.
Gasparini, F., Skobo, T., Benato, F., Gioacchini, G., Voskoboynik, A., Carnevali, O., … Dalla Valle, L. (2016). Characterization of Ambra1 in asexual cycle of a non-vertebrate chordate, the colonial tunicate Botryllus schlosseri, and phylogenetic analysis of the protein group in Bilateria. Molecular Phylogenetics and Evolution, 95, 46–57.
Voskoboynik, A., & Weissman, I. L. (2015). Botryllus schlosseri, an emerging model for the study of aging, stem cells, and mechanisms of regeneration. INVERTEBRATE REPRODUCTION & DEVELOPMENT, 59, 33–38.
Stolfi, A., Sasakura, Y., Chalopin, D., Satou, Y., Christiaen, L., Dantec, C., … Lemaire, P. (2015). Guidelines for the Nomenclature of Genetic Elements in Tunicate Genomes. GENESIS, 53(1), 1–14.
Manni, L., Gasparini, F., Hotta, K., Ishizuka, K. J., Ricci, L., Tiozzo, S., … Dauga, D. (2014). Ontology for the Asexual Development and Anatomy of the Colonial Chordate Botryllus schlosseri. PLOS ONE, 9(5).
Griggio, F., Voskoboynik, A., Iannelli, F., Justy, F., Tilak, M.-K., Xavier, T., … Gissi, C. (2014). Ascidian Mitogenomics: Comparison of Evolutionary Rates in Closely Related Taxa Provides Evidence of Ongoing Speciation Events. GENOME BIOLOGY AND EVOLUTION, 6(3), 591–605.
Rinkevich, Y., Voskoboynik, A., Rosner, A., Rabinowitz, C., Paz, G., Oren, M., … Rinkevich, B. (2013). Repeated, Long-Term Cycling of Putative Stem Cells between Niches in a Basal Chordate. DEVELOPMENTAL CELL, 24(1), 76–88.
Voskoboynik, A. (2009). Chimerism a natural ability to tolerate kin, evolutionary traits connecting mammalian and protochordates. ISJ-INVERTEBRATE SURVIVAL JOURNAL, 6(1), S9–S20.
Voskoboynik, A., Rinkevich, B., & Weissman, I. L. (2009). Stem Cells, Chimerism and Tolerance: Lessons from Mammals and Ascidians. Stem Cells in Marine Organisms (pp. 281–308). Springer Netherlands.
Tiozzo, S., Voskoboynik, A., Brown, F. D., & De Tomaso, A. W. (2008). A conserved role of the VEGF pathway in angiogenesis of an ectodermally-derived vasculature. DEVELOPMENTAL BIOLOGY, 315(1), 243–255.
Rosner, A., Rabinowitz, C., Moiseeva, E., Voskoboynik, A., & Rinkevich, B. (2007). BS-Cadherin in the colonial urochordate Botryllus schlosseri: One protein, many functions. DEVELOPMENTAL BIOLOGY, 304(2), 687–700.
Nyholm, S. V., Passegue, E., Ludington, W. B., Voskoboynik, A., Mitchel, K., Weissman, I. L., & De Tomaso, A. W. (2006). fester, a Candidate allorecognition receptor from a primitive chordate. IMMUNITY, 25(1), 163–173.
Voskoboynik, A., Rinkevich, B., WEISS, A., Moiseeva, E., & Reznick, A. Z. (2004). Macrophage involvement for successful degeneration of apoptotic organs in the colonial urochordate Botryllus schlosseri. JOURNAL OF EXPERIMENTAL BIOLOGY, 207(14), 2409–2416.
Voskoboynik, A., Reznick, A. Z., & Rinkevich, B. (2002). Rejuvenescence and extension of an urochordate life span following a single, acute administration of an anti-oxidant, butylated hydroxytoluene. MECHANISMS OF AGEING AND DEVELOPMENT, 123(9), 1203–1210.