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1. 发明申请

US20140193910A1 METHODS FOR PRODUCING PANCREATIC PRECURSOR CELLS AND USES THEREOF 审中-公开
标题翻译：生产胰腺前体细胞的方法及其用途
公开(公告)号：US20140193910A1
公开(公告)日：2014-07-10
申请号：US14125665
申请日：2012-06-15
申请人： James L. Sherley , Jean-Francois Pare
发明人： James L. Sherley , Jean-Francois Pare
IPC分类号： C12N5/071
CPC分类号： C12N5/0678 , A61K35/39 , C12N2500/40 , C12N2509/00
摘要： The present invention is directed to methods for readily propagating somatic pancreatic precursor cells. The methods comprise isolating cells from intact pancreatic samples and enhancing guanine nucleotide (GNP) biosynthesis in cultures comprising these cells, thereby expanding guanine nucleotide pools. This in turn conditionally suppresses asymmetric cell kinetics in the cells, thereby generating pancreatic precursor cells.
摘要翻译：本发明涉及容易繁殖体细胞胰腺前体细胞的方法。该方法包括从完整的胰腺样品中分离细胞并增强包含这些细胞的培养物中的鸟嘌呤核苷酸（GNP）生物合成，从而扩大鸟嘌呤核苷酸库。这又有条件地抑制细胞中的不对称细胞动力学，从而产生胰腺前体细胞。

2. 发明申请

US20090142760A1 Nucleic Acid Sequences Associated with Cell States 有权
标题翻译：与细胞状态相关的核酸序列
公开(公告)号：US20090142760A1
公开(公告)日：2009-06-04
申请号：US12063182
申请日：2006-08-08
申请人： James L. Sherley , Min-Soo Noh
发明人： James L. Sherley , Min-Soo Noh
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/158
摘要： The present invention is directed to nucleic acid sequences whose expression is associated with different cell states, including nucleic acid sequences whose expression is induced at least 100-fold, or alternatively upregulated, in cells exhibiting asymmetric self-renewal relative to other cells. The invention is also directed to nucleic acid sequences whose expression is induced at least 100-fold, or alternatively upregulated, in cells exhibiting symmetric self-renewal relative to other cells.
摘要翻译：本发明涉及其表达与不同细胞状态相关的核酸序列，包括在其相对于其他细胞显示不对称自我更新的细胞中，其表达被诱导至少100倍或可选地上调的核酸序列。本发明还涉及其表达在相对于其他细胞显示对称自我更新的细胞中被诱导至少100倍或可选地上调的核酸序列。

3. 发明授权

US09733236B2 Methods for determining the effect of an agent on tissue stem cells 有权
公开(公告)号：US09733236B2
公开(公告)日：2017-08-15
申请号：US14682384
申请日：2015-04-09
申请人： James L. Sherley
发明人： James L. Sherley
IPC分类号： G01N33/50
CPC分类号： G01N33/5014 , G01N33/502 , G01N33/5073
摘要： Herein, we describe a direct in vitro method that identifies agents that are toxic against natural human tissue stem cells. We provide a novel schedule for culturing any cell population containing homologous tissue stem cells that allows the number and cell kinetics of tissue stem cells, transient cells, and terminally differentiated cells within the population to be monitored. Using the passage schedule together with determination of a growth curve for the population, one can determine whether or not an agent is toxic to tissue stem cells, or to transient cells and/or terminal cells. The same method can also be used to identify agents that act positively on tissue stem cells and the other specific cell types.

4. 发明授权

US09081008B2 Detecting and counting tissue—specific stem cells and uses thereof 有权
标题翻译：检测和计数组织特异性干细胞及其用途
公开(公告)号：US09081008B2
公开(公告)日：2015-07-14
申请号：US13513289
申请日：2010-12-03
申请人： James L. Sherley
发明人： James L. Sherley
IPC分类号： G01N33/569 , G01N33/50
CPC分类号： G01N33/56966 , G01N33/5073 , G01N33/5076
摘要： This invention provides methods of determining the number and percent of tissue specific stem cells (TSSCs) in a sample of cells, a population of cells or a sample of tissue. The methods rely on detecting the pattern-specific asymmetric localization of asymmetric self-renewal associated (ASRA) proteins or cell cycle specific proteins (CSSP) in cell undergoing asymmetrical self-renewal, which is a characteristic of TSSCs. The methods can be applied to any situations in which the percent of TSSC is desired such as laboratory research on adult stem cells, in drug development tests, prognostic indicator and therapeutic index, as a diagnostic and prognostic indicator and in monitoring TSSC expansion, e.g., in cell manufacturing processes.
摘要翻译：本发明提供了确定细胞样品，细胞群或组织样品中组织特异性干细胞（TSSC）的数量和百分比的方法。该方法依赖于检测不对称自我更新相关（ASRA）蛋白或细胞周期特异性蛋白（CSSP）在经历不对称自我更新的细胞中的模式特异性不对称定位，这是TSSC的特征。该方法可以应用于需要TSSC的百分比，如成人干细胞的实验室研究，药物开发测试，预后指标和治疗指标，作为诊断和预后指标以及监测TSSC扩张的任何情况，例如，在细胞制造过程中。

5. 发明授权

US08759098B2 Method for cloning pluripotent stem cells 有权
标题翻译：克隆多能干细胞的方法
公开(公告)号：US08759098B2
公开(公告)日：2014-06-24
申请号：US13513612
申请日：2010-12-03
申请人： James L. Sherley
发明人： James L. Sherley
IPC分类号： C12N5/00 , C12N5/02 , C12N5/071
CPC分类号： C12N5/0696 , C12N2500/40 , C12N2500/90 , C12N2500/99 , C12N2502/13 , C12N2502/22 , C12N2517/02
摘要： Embodied herein are methods of reprogramming somatic cells or tissue stem cells to a more multipotent state or even a pluripotent state, the methods do not involve gene transfer of master transcription factor genes/proteins. The methods are also useful for rapid and efficient cloning of induced pluripotent stem cells after gene transfer of master transcription factor genes/proteins.
摘要翻译：本文所体现的是将体细胞或组织干细胞重新编程为更多能状态或甚至多能状态的方法，该方法不涉及主转录因子基因/蛋白质的基因转移。该方法也可用于快速有效地克隆主转录因子基因/蛋白基因转移后诱导的多能干细胞。

6. 发明申请

US20100086936A1 HEPATOCYTE PRECURSOR CELL LINES 有权
标题翻译： HEPATOCYTE PRECURSOR细胞系
公开(公告)号：US20100086936A1
公开(公告)日：2010-04-08
申请号：US12619107
申请日：2009-11-16
申请人： James L. Sherley , Hsuan-Shu Lee , Gracy G. Crane
发明人： James L. Sherley , Hsuan-Shu Lee , Gracy G. Crane
IPC分类号： C12Q1/68 , C12N5/071
CPC分类号： C12N5/0672 , C12N2500/40
摘要： The present invention is directed to methods for readily generating hepatocyte precursor cell lines that retain hepatocyte-specific functions after extensive in vitro culturing. The methods comprise isolating and culturing hepatocyte precursor cell lines under permissive culture conditions that suppress asymmetric cell kinetics and allow exponential growth of the precursor cells, followed by transferring the hepatocyte precursor cell lines to non-permissive culture conditions that allow expression of asymmetric cell kinetics and induce expression of hepatocyte-specific characteristics.
摘要翻译：本发明涉及容易产生在广泛体外培养后保留肝细胞特异性功能的肝细胞前体细胞系的方法。所述方法包括在抑制不对称细胞动力学并允许前体细胞的指数生长的许可培养条件下分离和培养肝细胞前体细胞系，随后将肝细胞前体细胞系转移至允许表达不对称细胞动力学的非允许培养条件，诱导肝细胞特异性表达。

7. 发明申请

US20150293077A1 METHODS FOR DETERMINING THE EFFECT OF AN AGENT ON TISSUE STEM CELLS 审中-公开
标题翻译：用于确定药物对组织干细胞的影响的方法
公开(公告)号：US20150293077A1
公开(公告)日：2015-10-15
申请号：US14682384
申请日：2015-04-09
申请人： James L. Sherley
发明人： James L. Sherley
IPC分类号： G01N33/50
CPC分类号： G01N33/5014 , G01N33/502 , G01N33/5073
摘要： Herein, we describe a direct in vitro method that identifies agents that are toxic against natural human tissue stem cells. We provide a novel schedule for culturing any cell population containing homologous tissue stem cells that allows the number and cell kinetics of tissue stem cells, transient cells, and terminally differentiated cells within the population to be monitored. Using the passage schedule together with determination of a growth curve for the population, one can determine whether or not an agent is toxic to tissue stem cells, or to transient cells and/or terminal cells. The same method can also be used to identify agents that act positively on tissue stem cells and the other specific cell types.
摘要翻译：在这里，我们描述了一种直接的体外方法，其识别对天然人组织干细胞具有毒性的药剂。我们提供了培养任何含有同源组织干细胞的细胞群的新时间表，其允许监测群体内组织干细胞，瞬时细胞和终末分化的细胞的数量和细胞动力学。使用通过方案和确定群体的生长曲线，可以确定试剂是否对组织干细胞或瞬时细胞和/或终末细胞有毒性。也可以使用相同的方法来鉴定对组织干细胞和其他特定细胞类型起积极作用的药剂。

8. 发明授权

US08404481B2 Hepatocyte precursor cell lines 有权
标题翻译：肝细胞前体细胞系
公开(公告)号：US08404481B2
公开(公告)日：2013-03-26
申请号：US12619107
申请日：2009-11-16
申请人： James L. Sherley , Hsuan-Shu Lee , Gracy G. Crane
发明人： James L. Sherley , Hsuan-Shu Lee , Gracy G. Crane
IPC分类号： C12N5/00 , C12N5/02 , C12N5/07 , C12N5/071
CPC分类号： C12N5/0672 , C12N2500/40
摘要： The present invention is directed to methods for readily generating hepatocyte precursor cell lines that retain hepatocyte-specific functions after extensive in vitro culturing. The methods comprise isolating and culturing hepatocyte precursor cell lines under permissive culture conditions that suppress asymmetric cell kinetics and allow exponential growth of the precursor cells, followed by transferring the hepatocyte precursor cell lines to non-permissive culture conditions that allow expression of asymmetric cell kinetics and induce expression of hepatocyte-specific characteristics.
摘要翻译：本发明涉及容易产生在广泛体外培养后保留肝细胞特异性功能的肝细胞前体细胞系的方法。所述方法包括在抑制不对称细胞动力学并允许前体细胞的指数生长的许可培养条件下分离和培养肝细胞前体细胞系，随后将肝细胞前体细胞系转移至允许表达不对称细胞动力学的非允许培养条件，诱导肝细胞特异性表达。

9. 发明授权

US07883891B2 Unique properties of stem cells 有权
标题翻译：干细胞的独特性质
公开(公告)号：US07883891B2
公开(公告)日：2011-02-08
申请号：US10483601
申请日：2002-07-17
申请人： James L Sherley , Joshua R. Merok
发明人： James L Sherley , Joshua R. Merok
IPC分类号： C12N5/08
CPC分类号： C12Q1/6841 , C12Q2563/173 , C12Q2563/131 , C12Q2525/101
摘要： The present invention is directed to unique properties of stem cells, including methods to identify stem cell markers by identifying molecules associated specifically with chromosomes in stem cells. More particularly, we have discovered that somatic stem cells repeatedly inherit an entire complement of chromosomes that contain the same parental template DNA strands from one generation to the next. The present invention also provides methods related to diagnosis, prognosis, and treatments for cancer and aging in mammalian tissus, including human.
摘要翻译：本发明涉及干细胞的独特性质，包括通过鉴定与干细胞中的染色体特异性相关的分子来鉴定干细胞标记的方法。更具体地说，我们已经发现体细胞干细胞重复地继承了从一代到下一代含有相同亲本模板DNA链的染色体的整个补体。本发明还提供了与包括人在内的哺乳动物组织中的癌症和衰老的诊断，预后和治疗相关的方法。

10. 发明申请

US20120295351A1 METHOD FOR CLONING PLURIPOTENT STEM CELLS 有权
标题翻译：克隆肺癌干细胞的方法
公开(公告)号：US20120295351A1
公开(公告)日：2012-11-22
申请号：US13513612
申请日：2010-12-03
申请人： James L. Sherley
发明人： James L. Sherley
IPC分类号： C12N5/071
CPC分类号： C12N5/0696 , C12N2500/40 , C12N2500/90 , C12N2500/99 , C12N2502/13 , C12N2502/22 , C12N2517/02
摘要： Embodied herein are methods of reprogramming somatic cells or tissue stem cells to a more multipotent state or even a pluripotent state, the methods do not involve gene transfer of master transcription factor genes/proteins. The methods are also useful for rapid and efficient cloning of induced pluripotent stem cells after gene transfer of master transcription factor genes/proteins.
摘要翻译：本文所体现的是将体细胞或组织干细胞重新编程为更多能状态或甚至多能状态的方法，该方法不涉及主转录因子基因/蛋白质的基因转移。该方法也可用于快速有效地克隆主转录因子基因/蛋白基因转移后诱导的多能干细胞。

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