SHP2 Regulation of the Plasticity of Bone Marrow Osterix+ Stroma

SHP2 对骨髓 Osterix 基质可塑性的调节

• 批准号: 10701128
• 负责人: Wentian Yang
• 金额: $ 10万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10701128
• 关键词: Adipocytes; Adult; Affect; Age; B-Lymphocytes; Biology; Blood; Blood Cell Count; Blood Cells; Blood Circulation; Blood Vessels; Bone Marrow; Bone marrow failure; CD19 gene; CD34 gene; Cell Lineage; Cell Survival; Cells; Cellular biology; Characteristics; Common Lymphoid Progenitor; Data; Development; Embryo; Endothelium; Erythrocytes; Foundations; Frequencies; Genetic; Goals; Health; Hematological Disease; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Homeostasis; Knowledge; Lymphocyte; Lymphoid; Lymphopoiesis; Megakaryocytes; Mesenchymal; Mesenchymal Differentiation; Modality; Molecular; Mus; Myelogenous; Myeloid Cells; Nature; Neonatal; Osteoblasts; Osteogenesis; Outcome Study; PTPN11 gene; PTPRC gene; Pericytes; Perinatal; Phenotype; Population; PubMed; Regulation; Reporter; Reporting; Role; SLAM family receptor; Skeletal Development; Sorting - Cell Movement; Stromal Cells; T-Lymphocyte; Testing; Text; Time; Tissues; United States National Library of Medicine; Work; Zinc Fingers; bone; cohort; granulocyte; hematopoietic differentiation; hematopoietic stem cell differentiation; innovation; leukemia; novel; novel marker; novel therapeutics; osteoblast differentiation; osteogenic; peripheral blood; postnatal; progenitor; promoter; skeletal; stem; stem cell survival; stem cells; transcription factor; tumor; tumorigenic; virtual

(PLEASE KEEP IN WORD, DO NOT PDF) This section must be no longer than 30 lines of text. It has been recently reported that the promoter of the master osteogenic transcription factor, OSTERIX, is active perinatally in hematopoietic cells, and that GFP+ blood cells circulate at low frequency in Tg(Osx-GFP:Cre) reporter mice. However, nothing is currently known about the significance of the hematopoietic cell-specific OSTERIX expression, and whether OSTERIX depletion might impact hematopoiesis. The work outlined in this proposal builds on the novel findings that Osx-GFP marks some BM and peripheral blood cells, and the number of these GFP+ blood cells decreases and disappears during development and maturation. Since OSTERIX expression and function in the hematopoietic system remain largely unknown, these findings together stimulate the hypothesis that OSTERIX is temporarily expressed in hematopoietic stem cells (HSCs) and that it is required for their survival, and/or lineage commitment and hematopoietic homeostasis. To test this novel hypothesis, we propose two specific Aims. In Aim 1, we will determine the dynamics of OSTERIX expression by quantifying GFP+ blood cells in embryonic, postnatal, and adult Tg(Osx-GFP:Cre) mice using FACS analysis. In Aim 2, we will determine the impact of OSTERIX depletion in HSCs on cell survival and multilineage differentiation using Tg(Mx1-Cre;Osxfx/fx) upon p(I)(C) induction. This innovative study will result in the first-ever description of OSTERIX’s regulatory role in the hematopoietic system and provide foundational information on the effect of OSTERIX dysregulation in blood. Successful completion of the work proposed will have a significant impact on our understanding of the hematopoietic regulation by OSTERIX and advance our knowledge about OSTERIX in the extraskeletal tissues.

（请保存在WORD中，不要使用PDF格式）本部分的文本不得超过30行。