Collaborative Research: RECODE: Microfluidic and genetic technologies to direct and select retinal cell types from human induced pluripotent stem cell-derived retinal organoids

合作研究：RECODE：微流体和遗传技术从人类诱导多能干细胞衍生的视网膜类器官中指导和选择视网膜细胞类型

• 批准号: 2225476
• 负责人: Todd Sulchek
• 金额: $ 70.83万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2225476&HistoricalAwards=false
• 关键词: Collaborative; Research; RECODE; Microfluidic; genetic

The differentiation of cells is the result of a complicated set of processes. Most stem cell differentiation methods result in a mixture of desired and undesired cell types. Better understanding of key molecular control points of differentiation could decrease the generation of undesirable cells. That in turn could increase the effectiveness of cell-based therapies. Genetic and mechanical techniques will be employed to better understand the differentiation pathway resulting in retinal cells. The hope is that this will lead to new treatments for degenerative eye diseases. Biomanufacturing workforce development will also be supported in several ways. Graduate students will be trained in stem cell biology and bioengineering, undergraduate students will be provided research opportunities, and outreach to industry will be accomplished through the Center for Cell Manufacturing Technologies.Controlling human induced pluripotent stem cell (hiPSC) differentiation is a challenge. Cell molecular pathways are programmed to react to external cues. Most protocols depend to a great degree on spontaneous cell fate commitment. This often results in a heterogeneous mixture of tissue specific cell types, many of which are not needed, or detrimental, for regenerative cell replacement strategies. Applying microfluidic cell separation and geno-mechanical techniques will be evaluated for their ability to reliably direct differentiation of hiPSCs to retinal cells. The first objective is to develop genome-wide methods that use both cell differentiation and biomechanical properties as screens to target desired endpoints during retinal cell differentiation. This objective could uncover new target pathways that can be exploited during culture to regulate retinogenesis. The second objective is to use systems biology to identify master regulators of retinal cell differentiation These regulators will be validated by observing the effects of modulation of these pathways on differentiated retinal subtypes. A third objective is to use cell separation approaches coupled with novel markers to enhance the production of the proper proportion of rods to cones.This RECODE project is funded by the Engineering Biology and Health Cluster in the Division of Chemical, Bioengineering, Environmental, and Transport Systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞的分化是一组复杂过程的结果。大多数干细胞分化方法导致所需和不希望的细胞类型的混合物。更好地了解分化的关键分子控制点可以减少不良细胞的产生。反过来，这可能会提高基于细胞的疗法的有效性。将采用遗传和机械技术来更好地了解导致视网膜细胞的分化途径。希望这将导致退化性眼部疾病的新疗法。生物制造业劳动力发展也将通过多种方式得到支持。研究生将接受干细胞生物学和生物工程的培训，将提供研究机会，并通过细胞制造技术中心来实现对工业的研究。控制人类诱导的多能干细胞（HIPSC）分化是一个挑战。细胞分子途径被编程为对外部线索的反应。大多数协议在很大程度上取决于自发的细胞命运承诺。这通常会导致组织特异性细胞类型的异质混合物，其中许多细胞类型不需要或有害，用于再生细胞置换策略。将评估应用微流体细胞分离和机电技术，将评估其可靠地直接将hipsC与视网膜细胞进行直接分化的能力。第一个目标是开发全基因组方法，这些方法在视网膜细胞分化过程中同时使用细胞分化和生物力学特性作为筛选。该目标可能会发现新的目标途径，这些途径可以在培养过程中被利用以调节视网膜生成。第二个目标是使用系统生物学来识别视网膜细胞分化的主要调节因子，这些调节剂将通过观察这些途径对分化视网膜亚型的调节的影响来验证。第三个目标是使用连接和新标记的细胞分离方法来增强杆与锥体的适当产生。此重新编码项目由工程生物学和健康集群资助，用于化学，生物工程，环境和运输部。 Systems。该奖项反映了NSF的法定任务，并通过使用基金会的智力优点和更广泛的影响审查标准来评估值得支持。

项目成果

Correlating mechanical and gene expression data on the single cell level to investigate metastatic phenotypes

• DOI: 10.1016/j.isci.2023.106393
• 发表时间: 2023-03-23
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Young，Katherine M.;Xu，Congmin;Sulchek，Todd
• 通讯作者: Sulchek，Todd

Strain-dependent elastography of cancer cells reveals heterogeneity and stiffening due to attachment

癌细胞的应变依赖性弹性成像揭示了由于附着而产生的异质性和硬化

• DOI: 10.1016/j.jbiomech.2023.111479
• 发表时间: 2023
• 期刊: Journal of Biomechanics
• 影响因子: 2.4
• 作者: Xu, Wenwei;Kabariti, Saif;Young, Katherine M.;Swingle, Steven P.;Liu, Alan Y.;Sulchek, Todd
• 通讯作者: Sulchek, Todd