| 项目编号: | 1508950
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| 项目名称: | UNS:Role of Cell-Mediated ECM Remodeling in Pluripotent Stem Cell Differentiation |
| 作者: | Sean Palecek
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| 承担单位: | University of Wisconsin-Madison
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| 批准年: | 2014
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| 开始日期: | 2015-06-01
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| 结束日期: | 2018-05-31
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| 资助金额: | USD350000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | differentiation
; hpsc differentiation
; hpsc
; ecm remodeling
; ecm
; candidate cell-synthesized ecm protein
; project
; normal cell
; stem cell science
; stem cell
; skin cell
; human pluripotent stem cell
; extracellular matrix remodeling
; vascular endothelial cell
; ecm synthesis
; endothelial cell
; stem cell engineer
; ecm component
; heart cell
; brain cell
; crispr/cas9-mediated ecm gene knockout experiment
; cell remodeling
; cell environment
; stem cell differentiation
; stem cell differentiation fate
; cell fate decision
; blood vessel cell
; matrix remodeling
; hypothesis
; extracellular matrix
; specialized cell type
; stem cell-derived cell
|
| 英文摘要: | 1508950
Palecek, Sean P.
A significant roadblock impeding realization of the promise of human pluripotent stem cells (hPSCs) is the inability to efficiently biomanufacture normal cells from hPSCs, in a large part resulting from an incomplete understanding of how hPSCs decide how to differentiate to more specialized cell types. These cell fate decisions are influenced by chemical and mechanical signals present in the cell environment. This project will investigate how cell remodeling of their extracellular matrix (ECM) environment affects differentiation to various testbed lineages including heart cells, blood vessel cells, brain cells, and skin cells. This deeper understanding of mechanisms of stem cell differentiation will then inform design of more efficient, defined protocols for guiding stem cells to cells in desired lineages. Thus, the project outcomes will have direct implications on producing stem cell-derived cells and tissues at lab scale or in biomanufacturing applications.
This project will test the hypothesis that extracellular matrix remodeling by hPSCs during differentiation is a key regulator of stem cell differentiation fate. The project will identify novel autocrine/paracrine mechanisms of regulation of hPSC fate via ECM remodeling, and demonstrate the importance of designing materials and scaffolds that enhance or inhibit ECM remodeling during hPSC differentiation. To test this hypothesis, proteomic analysis will be used to identify ECM components produced during hPSC directed differentiation to cardiomyocytes, endothelial cells, neurons, and keratinocytes. These experiments will identify candidate cell-synthesized ECM proteins that regulate specific hPSC differentiation fates. To test the prediction that ECM synthesis is necessary for efficient directed differentiation, CRISPR/Cas9-mediated ECM gene knockout experiments will be employed to assess how inhibiting matrix production affects hPSC differentiation to cardiomyocytes, vascular endothelial cells, neurons, and keratinocytes. Finally, to test the hypothesis that matrix remodeling via proteolytic degradation of ECM affects hPSC differentiation efficiency, matrix metalloprotease expression and activity will be monitored during directed differentiation, then chemical inhibitors and genetic knockouts will be used to quantify the contributions of these proteases during directed differentiation. Education and outreach activities described in this proposal will also train stem cell engineers at the graduate and undergraduate levels, and will provide outreach to K-12 students, K-12 teachers, undergraduate students, and the general public on technical, ethical, and political aspects of stem cell science and engineering.
This award by the Biotechnology and Biochemical Engineering Program of CBET is co-funded by the Biomaterials Program of the Division of Materials Research. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/94604
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Sean Palecek. UNS:Role of Cell-Mediated ECM Remodeling in Pluripotent Stem Cell Differentiation. 2014-01-01.
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