Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development.
Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development.
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人类发育过程中造血干/祖细胞谱系特化和基因调控网络的转变。
DOI：
10.1016/j.celrep.2021.109698
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发表时间：
2021-09-14
期刊：
影响因子：
8.8
通讯作者：
Thongjuea S
中科院分区：
文献类型：
--
作者：
Roy A;Wang G;Iskander D;O'Byrne S;Elliott N;O'Sullivan J;Buck G;Heuston EF;Wen WX;Meira AR;Hua P;Karadimitris A;Mead AJ;Bodine DM;Roberts I;Psaila B;Thongjuea S
人类造血是一个动态的过程，在怀孕后18-21天开始在子宫内。如果我们要了解血液系统疾病的起源，了解造血的部位和阶段特异性变化是很重要的，其中许多发生在人类寿命的特定点。为了揭示造血干/祖细胞（HSPC）在人类个体发育过程中的变化及其潜在的基因调控机制，我们比较了来自5种不同组织的57，489个HSPC，这些组织跨越了人类一生中的4个发育阶段。单细胞转录组学分析确定了细胞结构和基因调控网络中的重要位点和发育阶段特异性转变。造血干细胞在个体发育过程中表现出从循环到静止的进展和增加的炎症信号传导。我们证明了这个数据集的效用，了解异常造血通过比较两种癌症，目前在不同的时间点在出生后的生活-青少年骨髓单核细胞白血病，儿童癌症，骨髓纤维化，这是典型的老年人。在人类发育的4个阶段中采集> 57，000个造血细胞基因调控网络支持个体发育过程中谱系特化的变化干细胞显示细胞周期和炎症信号传导的进行性变化资源使人们能够理解特定年龄时出现的造血疾病Roy et al.使用单细胞转录组学比较人类个体发育过程中多种组织的造血干/祖细胞（HSPC）的谱系特化和基因调控网络。与来自两种血液癌症的HSPC的比较证明了数据集对于理解疾病过程和年龄特异性血液恶性肿瘤的出现的实用性。
Human hematopoiesis is a dynamic process that starts in utero 18–21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identifies significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Hematopoietic stem cells show progression from cycling to quiescence and increased inflammatory signaling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct time points in postnatal life—juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults. Sampling of >57,000 hematopoietic cells over 4 stages of human development Gene regulatory networks underpin changes in lineage specification through ontogeny Stem cells show progressive changes in cell cycling and inflammatory signaling Resource enables understanding of hematopoietic disorders presenting at specific age Roy et al. use single-cell transcriptomics to compare lineage specification and gene regulatory networks of hematopoietic stem/progenitor cells (HSPCs) from multiple tissues over human ontogeny. Comparison to HSPCs from two blood cancers demonstrates the utility of the dataset for understanding disease processes and the emergence of age-specific blood malignancies.
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影响因子：
16.6
作者：
Grover A;Sanjuan-Pla A;Thongjuea S;Carrelha J;Giustacchini A;Gambardella A;Macaulay I;Mancini E;Luis TC;Mead A;Jacobsen SE;Nerlov C
通讯作者：
Nerlov C
影响因子：
24.8
作者：
Drissen, Roy;Thongjuea, Supat;Nerlov, Claus
通讯作者：
Nerlov, Claus
影响因子：
20.3
作者：
Hua, Peng;Roy, Noemi;Davies, James O. J.
通讯作者：
Davies, James O. J.
DOI：
10.1084/jem.20111490
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dykstra B;Olthof S;Schreuder J;Ritsema M;de Haan G
通讯作者：
de Haan G
DOI：
10.1084/jem.20180853
发表时间：
2021-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Louka E;Povinelli B;Rodriguez-Meira A;Buck G;Wen WX;Wang G;Sousos N;Ashley N;Hamblin A;Booth CAG;Roy A;Elliott N;Iskander D;de la Fuente J;Fordham N;O'Byrne S;Inglott S;Norfo R;Salio M;Thongjuea S;Rao A;Roberts I;Mead AJ
通讯作者：
Mead AJ