PROJECT 1: Germ Cell Differentiation from Human iPSCs and hEScs
项目 1:人类 iPSC 和 hESc 的生殖细胞分化
基本信息
- 批准号:8638812
- 负责人:
- 金额:$ 32.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-01 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AZF1 geneAddressAdultAgeAnimal ModelBiological ModelsCell Differentiation processCell LineCellsCellular biologyCharacteristicsChromosome DeletionChromosome SegregationChromosomes, Human, YClinicClinicalClinical ResearchComplexCouplesDataDefectDeletion MutationDerivation procedureDevelopmentDiagnosticDissectionDrosophila genusDrosophila melanogasterExperimental GeneticsFailureFamily memberFemaleFrequenciesGene DosageGene ExpressionGene FamilyGenesGeneticGenetic EpistasisGenomeGerm CellsGerm LinesHaploidyHumanHuman DevelopmentHuman GeneticsHuman GenomeHuman IdentificationsIn VitroInfertilityInterventionIntracytoplasmic Sperm InjectionsInvestmentsLesionLinkMaintenanceMapsMeiosisMethodsMethylationMolecular GeneticsMorphogenesisMusMutagenesisMutationOocytesPartner in relationshipPathologyPathway interactionsPatternPhenotypePlatelet Factor 4Pluripotent Stem CellsProductionPropertyProteinsProtocols documentationPublishingQuality of lifeRNA-Binding ProteinsRegenerative MedicineRelative (related person)ResearchRoleScientific Advances and AccomplishmentsSertoli cell only syndromeSomatic CellSpermatogenesisStagingSystemTestingTherapeuticTranslationsTransplantationTurner&aposs SyndromeUniversitiesVariantWomanY ChromosomeYeastsbaseclinical applicationdata modelingdeletion analysisdesignexperimental analysisflygain of functiongene functiongene interactiongenetic analysisgenetic varianthuman embryonic stem cellhuman embryonic stem cell linehuman femalehuman maleimprintin vivoinduced pluripotent stem cellloss of function mutationmalemennovelnovel diagnosticsoverexpressionpluripotencysexsperm cellstem cell biologysuccesstooltranscription factor
项目摘要
A. Significance
A1. Infertility. Historically, the quality of life of infertile couples has been greatly diminished by the loss of
opportunity to conceive. However, in recent years, novel clinical interventions such as intracytoplasmic sperm
injection have dramatically changed the outlook for some couples, particularly those with severe forms of
infertility[23]. In parallel with clinical successes, there have also been ground-breaking scientific advances
including sequencing of the human genome, derivation of human embryonic stem cell (hESC) lines, and
reprogramming of adult human somatic cells to pluripotency[24-28]. Together, these advances now allow us to
overcome two historically-insurmountable limitations in studies of human development: the Inaccessibility of
early human development to exploration and the genetic-intractability of the genome during development.
A2. Need to study human germ cell development. 10-15% of couples are infertile, yet little is known of
underlying pathologies in men and women with poor germ cell production. Here, we propose to extend our
previous studies in order to permit genetic analysis of human germ cell development and thus, enable novel
basic and clinical studies and applications. There are several unique aspects to human germ cell development
that merit this investment. First, genes and dosages required for human germ cell development differ from
those of mice, including both autosomal and sex chromosomal genes and dosages[6,29-34]. Second, humans are
rare among species in that infertility is common, with half of all cases linked to faulty germ cell development[35].
Moreover, pathologies associated with meiotic errors are numerous in humans relative to other species, with
errors in meiotic chromosome segregation occurring in as many as 5-30% of human germ cells depending on
sex and age[36]. This is in contrast to frequencies of 1/10000 cells in yeast, 1/1000 cells in flies, and 1/100 cells
in mice. With recent advances, we now have the ability to incorporate new strategies in order to examine the
specifics of human germ cell development. This will allow us to derive full benefit from the wealth of data from
model systems such as the fly and the mouse, to begin to understand the complex genetics of human germ
cell formation and differentiation. In seeking to understand germ cell biology, we also acknowledge that the
ability to contribute to the germ line is a fundamental property that distinguishes pluripotent stem cells. For
example, Han and colleagues recently demonstrated that by addition of a 5th factor to the commonly-used 4
factor mixture for reprogramming, ability to contribute to the germ line was significantly increased[37]. This was in
spite of the fact that IPSCs derived from 5 factor-reprogramming were indistinguishable from standard iPSCs
or mESCs in gene expression and markers of pluripotency. Thus, the research proposed here allows us to
address fundamental questions regarding our germ line origins, function, and pathology and lays the
groundwork for designing rational therapeutics and diagnostics to inform clinical decisions based on data
obtained from model organisms, human genetic studies and direct experimental analysis of human germ cells.
It also contributes to the related field of pluripotent stem cell biology and regenerative medicine.
A.意义
A1.不孕从历史上看,不孕夫妇的生活质量已经大大降低了损失的,
有机会怀孕。然而,近年来,新的临床干预措施,如胞浆内精子,
注射大大改变了一些夫妇的前景,特别是那些严重的形式,
不孕症[23]。在临床成功的同时,也有突破性的科学进步
包括人类基因组的测序,人类胚胎干细胞(hESC)系的衍生,以及
将成人体细胞重编程为多能性[24-28]。总之,这些进步现在使我们能够
克服人类发展研究中两个历史上不可逾越的局限性:
早期人类发展到探索和基因组在发展过程中的遗传困难。
A2.需要研究人类生殖细胞的发育。10-15%的夫妇是不育的,但很少有人知道
生殖细胞生成不良的男性和女性的潜在病理。在此,我们建议扩大我们的
为了允许对人类生殖细胞发育进行遗传分析,
基础和临床研究及应用。人类生殖细胞发育有几个独特的方面
值得我们投资首先,人类生殖细胞发育所需的基因和剂量不同于
小鼠的那些,包括常染色体和性染色体基因和剂量[6,29 -34]。第二,人类是
在物种中罕见的是,不育是常见的,一半的病例与生殖细胞发育缺陷有关[35]。
此外,相对于其他物种,与减数分裂错误相关的病理在人类中很多,
减数分裂染色体分离错误发生在多达5-30%的人类生殖细胞中,这取决于
年龄与性别[36]这与酵母中的1/10000细胞、苍蝇中的1/1000细胞和
对小鼠随着最新的进展,我们现在有能力采用新的策略来检查
人类生殖细胞发育的细节。这将使我们能够充分受益于以下方面的丰富数据:
果蝇和小鼠等模型系统,从而开始了解人类生殖细胞的复杂遗传学
细胞形成和分化。在寻求了解生殖细胞生物学,我们也承认,
对生殖系有贡献的能力是区分多能干细胞的基本特性。为
例如,Han和他的同事最近证明,通过在常用的4个因子上增加第5个因子,
因子混合物的重编程,有助于生殖系的能力显着增加[37]。这是在
尽管事实上来源于5因子重编程的IPSC与标准的IPSC没有区别,
或mESC的基因表达和多能性标记。因此,这里提出的研究使我们能够
解决有关我们的生殖系起源,功能和病理学的基本问题,并奠定了
为设计合理的治疗和诊断奠定基础,以根据数据做出临床决策
从模式生物、人类遗传学研究和人类生殖细胞的直接实验分析中获得。
它还有助于多能干细胞生物学和再生医学的相关领域。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Renee A Reijo Pera其他文献
PLURIPOTENT STEM CELLS FROM THE ADULT HUMAN TESTIS
- DOI:
10.1016/s0022-5347(09)61912-1 - 发表时间:
2009-04-01 - 期刊:
- 影响因子:
- 作者:
Nina Kossack;Juanito Meneses;Shai Shefi;Ha Nam Nguyen;Shawn Chavez;Cory Nicholas;Joerg Cromoll;Renee A Reijo Pera;Paul J Turek - 通讯作者:
Paul J Turek
Renee A Reijo Pera的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Renee A Reijo Pera', 18)}}的其他基金
Dissection of the transcriptional network of human primordial germ cells
人类原始生殖细胞转录网络的剖析
- 批准号:
9981316 - 财政年份:2019
- 资助金额:
$ 32.77万 - 项目类别:
Dissection of the transcriptional network of human primordial germ cells
人类原始生殖细胞转录网络的剖析
- 批准号:
10428453 - 财政年份:2019
- 资助金额:
$ 32.77万 - 项目类别:
Dissection of the transcriptional network of human primordial germ cells
人类原始生殖细胞转录网络的剖析
- 批准号:
10398894 - 财政年份:2019
- 资助金额:
$ 32.77万 - 项目类别:
Dissection of the transcriptional network of human primordial germ cells
人类原始生殖细胞转录网络的剖析
- 批准号:
9921212 - 财政年份:2019
- 资助金额:
$ 32.77万 - 项目类别:
CORE B: STANFORD CENTER FOR REPRODUCTIVE AND STEM CELL BIOLOGY
核心 B:斯坦福生殖和干细胞生物学中心
- 批准号:
8638817 - 财政年份:2014
- 资助金额:
$ 32.77万 - 项目类别:
Stanford University Center for Reproductive and Stem Cell biology
斯坦福大学生殖和干细胞生物学中心
- 批准号:
8249005 - 财政年份:2011
- 资助金额:
$ 32.77万 - 项目类别:
Stanford University Center for Reproductive and Stem Cell biology
斯坦福大学生殖和干细胞生物学中心
- 批准号:
8070899 - 财政年份:2011
- 资助金额:
$ 32.77万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 32.77万 - 项目类别:
Research Grant