Imaging the formation of an hematopoietic niche

造血生态位形成的成像

• 批准号: 10808347
• 负责人: STEPHEN Francis DINARDO
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10808347
• 关键词: Address; Adopted; Applications Grants; Architecture; Biological; Cells; Cis Tests; Communication; DNA Binding Domain; DNA Sequencing Facility; Data; Defect; Development; Dorsal; Drosophila genus; Embryo; Event; Gene Expression Profile; Genes; Health; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Homeostasis; Image; Imaging Device; Immune; Innate Immune System; Insecta; Investigation; Label; Letters; Macrophage; Maintenance; Mesoderm; Mesoderm Cell; Morphogenesis; Organ; Pattern; Population; Positioning Attribute; Process; Production; Property; RNA; Reagent; Regenerative Medicine; Regulation; Resolution; Role; Sampling; Series; Signal Transduction; Source; Specific qualifier value; Specificity; Testing; Testis; Time; Tissues; Transactivation; Transgenic Organisms; Visceral; Visualization; Work; antimicrobial; candidate identification; cell behavior; daughter cell; experimental study; follow-up; improved; in vivo; insight; interest; lymph nodes; migration; next generation sequencing; novel marker; optogenetics; progenitor; prospective; selective expression; single-cell RNA sequencing; spatial relationship; stem cell function; stem cell niche; stem cells; success; tool; virtual

Stem cells are necessary for tissue homeostasis, and are often localized to specialized niches that control their function. In this manner, niches control virtually all aspects of stem cell dynamics, properties essential to tissue maintenance. Recent work has shown that precise cellular architecture is important in order for a niche to communicate with fidelity to the stem cells it controls. A major issue is that the field does not fully understand how niches are initially formed in a tissue, nor the key cell biological steps that cause a group of cells to create an effective niche, nor how that organization impacts stem cell regulation. Our lab recently made significant advances on such questions working on the testis niche. In particular we used live-imaging to define the dynamic steps in Drosophila gonadal niche assembly. These observations led directly to a series of experiments revealing a mechanistic understanding of the assembly of this niche. Insect hematopoiesis closely parallels our innate immune system, using several conserved factors important for specifying macrophage-like and anti-microbial-producing cells. The progenitors for these immune cells are controlled by a niche called the Posterior Signaling Center (PSC). Work of others using fixed embryos and end-point analysis showed that the PSC is derived from a cell cluster that must migrate to take up its proper position and begin functional as a niche. How the pro-niche cells navigate to the correct position and assemble into a functional niche is unknown. We propose here to develop tools to address these questions. We will build tools to lineage-label the PSC at an early-enough stage to visualize its construction in vivo. This includes the construction of transgenic lines that should confer spatial and temporal optogenetic control for labeling and real-time visualization. These same tools would enable follow-up experiments to expore the mechanisms underlying niche assembly. We will additionally profile the transcriptional landscape of PSC cells in order to identify new markers aiding investigation of PSC morphogenesis. Collectively, our approaches should provide us with the reagents and preliminary results to support a substantive, longer-term grant proposal addressing underlying mechanisms directly.

干细胞是组织内稳态所必需的，并且通常定位于控制其生长的特殊壁龛