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Gene Regulatory Control of Immune Ce...
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Schrankel, Catherine.
Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva./
作者:
Schrankel, Catherine.
面頁冊數:
1 online resource (219 pages)
附註:
Source: Dissertation Abstracts International, Volume: 79-03(E), Section: B.
標題:
Immunology. -
電子資源:
click for full text (PQDT)
ISBN:
9780355530018
Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva.
Schrankel, Catherine.
Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva.
- 1 online resource (219 pages)
Source: Dissertation Abstracts International, Volume: 79-03(E), Section: B.
Thesis (Ph.D.)--University of Toronto (Canada), 2017.
Includes bibliographical references
Hematopoietic systems in mammals have been the focus of intense study. However, complications such as paralog compensation among transcription factor genes in complex vertebrate models can make it difficult to characterize gene regulatory networks (GRNs) for immune cell differentiation in detail, especially in vivo. Simple invertebrates can provide systems-level models to explore GRN function as it directs development in the intact organism. The sea urchin (Strongylocentrotus purpuratus) is an emerging model for such studies. Larval immunocytes are patterned in the mesoderm at the blastula stage. Immunocyte precursors express single gene orthologs of vertebrate hematopoietic factors, including GATA-1,-2, 3 factors, Scl/Tal2/Lyl1, and the E-proteins (E2A/HEB/E2-2). Genome analyses also reveal a complex system of immune receptors and effectors.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9780355530018Subjects--Topical Terms:
592892
Immunology.
Index Terms--Genre/Form:
554714
Electronic books.
Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva.
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Gene Regulatory Control of Immune Cell Specification and Differentiation in the Sea Urchin Embryo and Larva.
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Hematopoietic systems in mammals have been the focus of intense study. However, complications such as paralog compensation among transcription factor genes in complex vertebrate models can make it difficult to characterize gene regulatory networks (GRNs) for immune cell differentiation in detail, especially in vivo. Simple invertebrates can provide systems-level models to explore GRN function as it directs development in the intact organism. The sea urchin (Strongylocentrotus purpuratus) is an emerging model for such studies. Larval immunocytes are patterned in the mesoderm at the blastula stage. Immunocyte precursors express single gene orthologs of vertebrate hematopoietic factors, including GATA-1,-2, 3 factors, Scl/Tal2/Lyl1, and the E-proteins (E2A/HEB/E2-2). Genome analyses also reveal a complex system of immune receptors and effectors.
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In my thesis I sought to 1) characterize immune cell terminal differentiation genes in more detail, 2) characterize the role of E-protein transcription factor splice variants driving the emergence of distinct mesodermal cell types, and 3) characterize the later expression of key transcription factors in maintaining larval immunocyte populations. I identified two markers: a thioester ?-macroglobulin like protein, Tecp2, and MacpfA2. MacpfA2 is part of a multi-gene family of 22 perforin-related effectors. Phylogenetic and expression analyses of the Macpf family identified eight sub-families that exhibit differential expression domains and transcriptional responses to infection across embryonic and adult tissues and cells.
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Two isoforms of SpE-protein were identified in immunocyte precursors: a longer canonical (Can) form and a truncated alternative (Alt) form that initiates from a unique first exon. SpE-Alt shares genomic organization and sequence conservation with the HEB and E2-2 vertebrate paralogs. SpE-Alt is required for immunocyte development and functions in a novel cis-regulatory mechanism between the two isoforms. A second isoform of SpGATA123 was also identified. A short isoform is predominant in immunocyte precursors and adult coelomocytes, whereas a longer form is expressed in larval endoderm. SpGATA123-S perturbation affects immunoctye migration and the expression of MacpfA2 . SpGATA123-S and other early regulators of immunocyte specification re-emerge in the coelomic pouches of the feeding larva.
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These studies in the sea urchin have reinforced the hypothesis that although cell morphology and terminal effectors diversify rapidly among different animals, deep homology exists at the level of primitive hemocyte development across deuterostomes. Aspects of these systems are re-deployed in definitive stages of hematopoiesis. In sum, simple animal models offer tractable systems for studying the regulatory machinery governing immune cell emergence in vivo. This provides a foundation for comparative GRN investigations that will improve our understanding of the evolution of immune systems across phyla.
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