Lymphopoietic development in the extra-embryonic yolk sac

胚胎外卵黄囊的淋巴细胞发育

• 批准号: 8389561
• 负责人: Mervin C. YODER
• 金额: $ 33.26万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-23 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8389561
• 关键词: Address; Adult; Antibodies; Aorta; Appearance; Autoimmune Diseases; B-Lymphocytes; Blood Cells; Blood Circulation; Blood flow; Bone Marrow; Calcium; Cardiac; Cardiac Myocytes; Cell Line; Cells; Coculture Techniques; Data; Development; Embryo; Erythrocytes; Extrahepatic; Fetal Liver; Goals; Gonadal structure; Greater sac of peritoneum; Growth; Growth Factor; Hematologist; Hematopoietic; Hematopoietic stem cells; Home environment; Homing; Human Development; In Vitro; Knockout Mice; Liver; Lymphocyte; Lymphoid; Lymphoid Cell; Lymphopoiesis; Marrow; Megakaryocytes; Mesonephric structure; Modeling; Molecular; Mus; Organ; Paraaortic; Pathway interactions; Population; Production; Proteins; Reporting; Seeds; Signal Pathway; Site; Sodium; Stem cells; Stromal Cells; Time; Wild Type Mouse; Work; Yolk Sac; fetal; human subject; in vivo; innovation; leukemia; macrophage; mutant; novel; novel strategies; prevent; progenitor

PROJECT SUMMARY/ABSTRACT The overall goal of the present work is to determine the mechanisms that permit the emergence of B lymphoid cells in the extraembryonic yolk sac and the para aortic splanchnopleura (P-Sp) and facilitate the homing of these cells into the peritoneal cavity. Though the extraembryonic yolk sac is the first site of primitive red blood cell, megakaryocyte, and macrophage production, it is controversial whether it is a site of B lymphoid emergence. An intraembryonic site, the aorta-gonad-mesonephros (AGM) region derived from the P-Sp, is currently recognized as the first site of production of HSCs capable of repopulating the hematopoietic compartment of lethally irradiated adult mice and is reported to possess the potential to give rise to B lymphoid cells upon in vitro co-culture with a certain stromal cell line. However, after the systemic circulation has commenced, it remains unclear and unproven whether the B cell progenitors are moving from the yolk sac into the P-Sp or vice versa. Indeed, the most formidable obstacle encountered when attempting to define the onset of B lymphopoiesis in the developing murine embryo, is the onset of cardiac contractions and establishment of the circulation. We have developed a novel approach that permits determination of exactly where and when hematopoietic cells emerge in the yolk sac and P-Sp. Ncx1 encodes a sodium-calcium exchange protein that is expressed only in cardiomyocytes through embryonic day (E) 11.0. Embryos lacking Ncx1 are unable to initiate cardiac contractions preventing the onset of the systemic circulation. Lack of blood flow is initially tolerated without evidence of maldevelopment, however embryos demonstrate growth retardation by E10.0 and die by E11.0. Using Ncx1 mutant and wild type (WT) mice, we have recently reported that all hematopoietic definitive progenitor cells that seed the E 10.0 fetal liver are yolk sac-derived. We have also reported that the potential for forming B lymphoid cells is present in the E 9.5 yolk sac and P-Sp of wild type and Ncx1 null mice; confirming that B lymphoid cells arise autonomously in the yolk sac and P-Sp. A host of questions now emerge that we address in the following aims: Aim 1: To delineate the temporal and spatial emergence of B lymphoid cells in the yolk sac and P-Sp and to define B cell specification to B1 and/or B2 lymphoid lineages from the emergent cells in these sites. Aim 2: To define the growth factor signaling pathways required for yolk sac and P-Sp B lymphopoiesis. Aim 3: Define the molecular pathway for yolk sac and P-Sp derived B cell homing to the peritoneal cavity. These studies will define the mechanism of B lymphocyte emergence, determine whether differences in B cell specification are intrinsic and restricted, and may clarify the origin of the B1 lymphocytes that secrete natural antibodies; a population of cells important in human development of autoimmune diseases and leukemia.

项目总结/文摘

项目成果

Bone marrow engraftment but limited expansion of hematopoietic cells from multipotent germline stem cells derived from neonatal mouse testis.

骨髓移植，但来自新生小鼠睾丸的多能生殖干细胞的造血细胞扩增有限。

• DOI: 10.1016/j.exphem.2009.09.006
• 发表时间: 2009
• 期刊: Experimental hematology
• 影响因子: 2.6
• 作者: Yoshimoto,Momoko;Heike,Toshio;Chang,Hsi;Kanatsu-Shinohara,Mito;Baba,Shiro;Varnau,JosephT;Shinohara,Takashi;Yoder,MervinC;Nakahata,Tatsutoshi
• 通讯作者: Nakahata,Tatsutoshi

Phenotypic and functional characterization of endothelial colony forming cells derived from human umbilical cord blood.

• DOI: 10.3791/3872
• 发表时间: 2012-04
• 期刊: Journal of visualized experiments : JoVE
• 作者: Nutan Prasain;J. L. Meador;Mervin C Yoder

Novel methods for determining hematopoietic stem and progenitor cell emergence in the murine yolk sac.

确定小鼠卵黄囊中造血干细胞和祖细胞出现的新方法。

• DOI: 10.1387/ijdb.103118cl
• 发表时间: 2010
• 期刊: The International journal of developmental biology
• 作者: Lux,ChristopherT;Yoder,MervinC
• 通讯作者: Yoder,MervinC

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

• DOI: 10.1161/circulationaha.114.009124
• 发表时间: 2014-05-27
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Alphonse RS;Vadivel A;Fung M;Shelley WC;Critser PJ;Ionescu L;O'Reilly M;Ohls RK;McConaghy S;Eaton F;Zhong S;Yoder M;Thébaud B
• 通讯作者: Thébaud B

Biomechanical forces promote embryonic haematopoiesis.

• DOI: 10.1038/nature08073
• 发表时间: 2009-06-25
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Adamo, Luigi;Naveiras, Olaia;Wenzel, Pamela L.;McKinney-Freeman, Shannon;Mack, Peter J.;Gracia-Sancho, Jorge;Suchy-Dicey, Astrid;Yoshimoto, Momoko;Lensch, M. William;Yoder, Mervin C.;Garcia-Cardena, Guillermo;Daley, George Q.
• 通讯作者: Daley, George Q.