概要: Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms leading to ageing remain elusive. We present a proteome-wide atlas of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) along with five other cell types that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified was assessed in a cohort of healthy human subjects from different age. As the HPCs became older, pathways in central carbon metabolism exhibited features reminiscent of the Warburg effect where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation revealed a reduced functionality and a bias towards myeloid differentiation at the expense of lymphoid development. Ageing caused significant alterations in the bone marrow niche too, such as functionality of the pathways involved in HPC homing and lineage differentiation. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models.
项目整体设计: Examination of myeloid- and lymphoid-primed sub-populations of HPCs across young and old donors
Bone marrow (BM) samples were harvested through puncture at the posterior iliac crest using a Yamshidi needle
处理方案:
BM aspirates were processed by FICOLL density fractionation for isolation of MNCs; stained with CD34-APC, CD45-FITC and CD14-PE; FACS-sorted and stored at -80C
提取方案:
Sequencing libraries from 192 single CD34+ cells per donor were produced based on the smart-seq2 protocol of Picelli et al. 2014 and the tagmentation procedure of Henning et al. 2018 with slight modifications as described in the publication.
建库方案:
-
测序信息
分子类型:
rRNA- RNA
库的片段类型:
SINGLE
库的链类型:
-; Reverse; Forward
测序平台:
ILLUMINA
测序仪型号:
Illumina NextSeq 500
链特异性:
Unspecific; Specific
样本
基本信息:
样本描述:
生物条件:
实验变量:
方案:
测序信息:
质量评估:
数据来源
GEN样本编号
GEN数据集编号
系列编号
项目编号
样本编号
样本名称
生物样本编号
样本访问号
实验访问号
释放时间
提交时间
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物种
种族
族裔
年龄
年龄单位
性别
来源名称
组织
细胞类型
细胞亚型
细胞系
疾病
疾病状态
发育阶段
突变/变异
表型
Condition Detail
生长方案
处理方案
提取方案
建库方案
分子类型
库的片段类型
链特异性
库的链类型
加标(Spike-In)
测序方法
测序平台
测序仪型号
细胞数
测序片段数
碱基数
平均测序片段长度_1
平均测序片段长度_2
唯一比对率
多重比对率
覆盖度
文章
Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline.