BIOREGULATION OF THE SPERMATOGONIAL STEM CELL LINEAGE

精原干细胞谱系的生物调节

• 批准号: 6636944
• 负责人: LAURA TRES
• 金额: $ 20.2万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6636944
• 关键词: Sertoli cells; actins; adenosine triphosphate; apoptosis; cell adhesion; cell adhesion molecules; cell cell interaction; cell differentiation; cell growth regulation; cell motility; cell proliferation; confocal scanning microscopy; cysteine endopeptidases; gelsolin; integrins; laboratory rat; mixed tissue /cell culture; polymerase chain reaction; sperm; spermatogenesis; stem cells; video microscopy

Spermatogenesis involves two critical events: 1. The detachment of spermatogonial cell progenies from basal lamina and Sertoli cell anchoring sites upon commitment to meiosis. 2. The elimination of nonviable spermatogenic cell progenies to regulate the balanced differentiation of spermatogenic cells into sperm. These developmental events imply a continuous morphological reorganization of the seminiferous epithelium whose structural and molecular details are unknown. Our overall hypothesis is that these two events are interrelated and under control by three interactive signaling pathways: 1. The integrin beta1 subunit of the alpha3beta1/alpha6beta1 complex. 2. Members of the disintegrin protein family. 3. Caspase-3, an essential mediator in apoptosis. An analysis of the molecular events linking these pathways has never been attempted. One objective of this proposal is to understand how Sertoli cell geometry controls the anchorage and viability of spermatogonial cell progenies and the second is to determine how the oscillatory movements of spermatogonial cells gate the execution of induced cell death. Our overall hypothesis is that Sertoli cell stretching and contraction govern the differentiation of the spermatogonial cell progeny and its translocation into the adluminal compartment of the seminiferous epithelium. We plan to: 1. Test the hypothesis that Sertoli cell geometry and beta1 integrin regulate the anchorage of spermatogonial cells to Sertoli cell surfaces. 2. Test the hypothesis that selected disintegrins can either disrupt or stabilize spermatogonial-Sertoli cell adhesion. 3. Test the hypothesis that enhanced spermatogonial oscillatory cell movements following Fas ligand-induced apoptosis are a prelude to imminent cell death initiated by the fragmentation of actin and gelsolin activated by apoptosis caspase-3. The significance of the proposed studies is two-fold: 1. To our knowledge, this is the first attempt to link Sertoli cell geometrical changes to the life-and-death of the spermatogonial cell progeny. 2. In the long range, the discovery of ways to prevent and modulate spermatogonial cell death may have significant therapeutic and anticonceptive potentials in humans.

精子发生涉及两个关键事件： 1. 精原细胞后代在减数分裂时从基底层和支持细胞锚定位点脱离。 2.消除不能存活的生精细胞后代，以调节生精细胞平衡分化为精子。这些发育事件意味着生精上皮的持续形态重组，其结构和分子细节尚不清楚。 我们的总体假设是，这两个事件是相互关联的，并受到三个相互作用的信号通路的控制： 1. alpha3beta1/alpha6beta1 复合物的整合素 beta1 亚基。 2.解整合蛋白家族的成员。 3. Caspase-3，细胞凋亡的重要介质。 从未尝试过对连接这些途径的分子事件进行分析。 该提案的一个目标是了解支持细胞几何形状如何控制精原细胞后代的锚定和活力，第二个目标是确定精原细胞的振荡运动如何控制诱导细胞死亡的执行。我们的总体假设是支持细胞的拉伸和收缩控制精原细胞后代的分化及其易位到生精上皮的腔内室。 我们计划： 1. 检验支持细胞几何形状和 beta1 整合素调节精原细胞与支持细胞表面的锚定的假设。 2. 检验以下假设：选定的解整合素可以破坏或稳定精原细胞-支持细胞的粘附。 3. 测试以下假设：Fas 配体诱导的细胞凋亡后精原细胞振荡细胞运动的增强是由细胞凋亡 caspase-3 激活的肌动蛋白和凝溶胶蛋白断裂引发的即将发生的细胞死亡的前奏。 这项研究的意义有两个： 1. 据我们所知，这是首次尝试将支持细胞的几何变化与精原细胞后代的生死联系起来。 2. 从长远来看，预防和调节精原细胞死亡的方法的发现可能对人类具有显着的治疗和避孕潜力。

项目成果

XY chromosomal bivalent: nucleolar attraction.

XY 染色体二价：核仁吸引力。

• DOI: 10.1002/mrd.20334
• 发表时间: 2005
• 期刊: Molecular reproduction and development.
• 作者: Tres,LauraL

Mouse round spermatids developed in vitro from preexisting spermatocytes can produce normal offspring by nuclear injection into in vivo-developed mature oocytes.

由预先存在的精母细胞在体外发育的小鼠圆形精子细胞可以通过将核注射到体内发育的成熟卵母细胞中来产生正常的后代。

• DOI: 10.1095/biolreprod.102.015099
• 发表时间: 2003
• 期刊: Biology of reproduction.
• 作者: Marh,Joel;Tres,LauraL;Yamazaki,Yukiko;Yanagimachi,Ryuzo;Kierszenbaum,AbrahamL
• 通讯作者: Kierszenbaum,AbrahamL

Primordial germ cells: What does it take to be alive?

• DOI: 10.1002/mrd.20056
• 发表时间: 2004-05-01
• 期刊: MOLECULAR REPRODUCTION AND DEVELOPMENT
• 影响因子: 2.5
• 作者: Tres, LL;Rosselot, C;Kierszenbaum, AL
• 通讯作者: Kierszenbaum, AL

The ADAM-integrin-tetraspanin complex in fetal and postnatal testicular cords.

• DOI: 10.1002/bdrc.20041
• 发表时间: 2005-06-01
• 期刊: Birth defects research. Part C, Embryo today : reviews
• 作者: Tres, Laura L;Kierszenbaum, Abraham L
• 通讯作者: Kierszenbaum, Abraham L

GMAP210 and IFT88 are present in the spermatid golgi apparatus and participate in the development of the acrosome-acroplaxome complex, head-tail coupling apparatus and tail.

• DOI: 10.1002/dvdy.22563
• 发表时间: 2011-03
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Kierszenbaum, Abraham L.;Rivkin, Eugene;Tres, Laura L.;Yoder, Bradley K.;Haycraft, Courtney J.;Bornens, Michel;Rios, Rosa M.
• 通讯作者: Rios, Rosa M.