The KAPP-Sen Tissue Mapping Center Collaborative

总体项目总结 该提案寻求建立Kapp-Sen组织映射中心协作(TMC)，作为细胞衰老网络：组织映射中心工作的一部分(RFA-RM-21-008)。我们的应用代表着一项多学科的合作努力，涉及六个领先的机构和老龄化研究项目，共同研究衰老细胞在不同健康人体组织中的分布和生物异质性，与细胞衰老网络(Sennet)的目标完全一致。 Kapp-Sen汇集了在健康人类肾脏框架内解决Sen-Net目标所需的技能、资源和观点。脂肪组织、胰腺和胎盘。鉴于我们有能力从提供Kapp样本的个人那里获得全层皮肤组织，我们可能会探索未来与TMC合作研究的可能性，这些TMC被选为主要关注皮肤的组织。我们的六个合作机构位于法明顿。CT(康涅狄格州大学健康，杰克逊基因组医学实验室)，波士顿(布里根妇女医院，乔斯林糖尿病中心)，罗切斯特。MN(梅奥诊所)和圣安东尼奥。德克萨斯州(UTHCSA)都是经过精心挑选的，因为他们对这一领域和这一努力做出了重要和独特的个人贡献。 我们的目标将通过以下几个目标实现： 目的1：协调跨Kapp-Sen TMC协作站点的研究活动，以支持SEN-Net目标，以定位健康人类肾脏、脂肪组织、胰腺和胎盘中的细胞衰老及其相关的分泌表型。 目的：从健康肾移植供体(肾脏、脂肪、皮肤)、剖宫产(胎盘、脐带、脂肪、皮肤)、门诊健康供体活体组织(脂肪、皮肤)、心脏不停跳脑死亡供体(全胰腺)和IIPD/Prodo(分散胰腺)获取组织。 目标3：生成与细胞衰老有关的高质量数据，包括所有组织中的scRNA-Seq、SnRNA-Seq、空间转录、免疫组织化学和端粒相关DDR焦点(TAFs) 目的4：与其他TMC、CODDC和NIH工作人员合作，执行创建人类细胞衰老模型所需的高水平综合数据分析。

PROJECT SUMMARY OVERALL This proposal seeks to establish the KAPP-Sen Tissue Mapping Center Collaborative (TMC) as part of the Cellular Senescence Network: Tissue Mapping Centers effort {RFA-RM-21-008). Our application represents a multidisciplinary collaborative effort involving six leading institutions and aging research programs working together to characterize the distribution and biological heterogeneity of senescent cells in different healthy human tissues in full alignment with the objectives of the Cellular Senescence Network {SenNet). KAPP-Sen brings together skills, resources and perspectives needed to address Sen-Net goals in the framework of the healthy human Kidney. Adipose tissues, Pancreas and Placenta. Given our ability to obtain full thickness skin tissues from individuals providing KAPP samples, we may explore the possibility of future collaborative studies with TMCs selected for their major focus on skin. Our six collaborating institutions located in Farmington. CT (UConn Health, Jackson Laboratory for Genomic Medicine), Boston {Brigham & Women's Hospital, Joslin Diabetes Center), Rochester. MN {Mayo Clinic) and San Antonio. TX {UTHCSA) have all been carefully selected for their essential and unique individual contributions to the field and this effort. Our objectives will be achieved through the following aims: Aim 1 : Coordinate research activities across KAPP-Sen TMC Collaborative sites in support of Sen-Net goals towards mapping cellular senescence and its associated secretory phenotype in the healthy human kidney, adipose tissues, pancreas and placenta. Aim 2: Obtain tissues from healthy kidney transplant donors {kidneys, fat, skin), C-section pregnancies {placenta, cord, fat, skin), outpatient healthy donor biopsies {fat, skin), beating heart brain dead donors {full pancreas) and IIPD/Prodo {dispersed pancreas). Aim 3: Generate highest quality data pertaining to cellular senescence including scRNA-Seq, snRNA-Seq, spatial transcriptomics, immunohistochemistry and Telomere-associated DDR foci {TAFs) in all tissues Aim 4: Perform high level integrative data analysis required for the creation of aUases of human cellular senescence in collaboration with other TMCs, CODDC and NIH staff.