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对年轻和年老小鼠造血干细胞及其祖细胞的蛋白质组学分析揭示了干细胞中的转录后调控。

Proteomic analysis of young and old mouse hematopoietic stem cells and their progenitors reveals post-transcriptional regulation in stem cells.

机构信息

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.

Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, United States.

出版信息

Elife. 2020 Nov 25;9:e62210. doi: 10.7554/eLife.62210.

DOI:10.7554/eLife.62210
PMID:33236985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7688314/
Abstract

The balance of hematopoietic stem cell (HSC) self-renewal and differentiation is critical for a healthy blood supply; imbalances underlie hematological diseases. The importance of HSCs and their progenitors have led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of hematopoiesis remains incompletely understood. Here we report a proteomics resource from mass spectrometry of mouse young adult and old adult mouse HSCs, multipotent progenitors and oligopotent progenitors; 12 cell types in total. We validated differential protein levels, including confirmation that Dnmt3a protein levels are undetected in young adult mouse HSCs until forced into cycle. Additionally, through integrating proteomics and RNA-sequencing datasets, we identified a subset of genes with apparent post-transcriptional repression in young adult mouse HSCs. In summary, we report proteomic coverage of young and old mouse HSCs and progenitors, with broader implications for understanding mechanisms for stem cell maintenance, niche interactions and fate determination.

摘要

造血干细胞（HSC）自我更新和分化的平衡对于健康的血液供应至关重要；这种平衡的失衡是血液疾病的基础。HSC 及其前体细胞的重要性导致了它们在基因组和转录组水平上的广泛特征描述。然而，造血的蛋白质组学仍未被完全理解。在这里，我们报告了从小鼠年轻成年和老年成年 HSC、多能祖细胞和寡能祖细胞中进行质谱分析的蛋白质组学资源；总共 12 种细胞类型。我们验证了差异蛋白水平，包括确认 Dnmt3a 蛋白水平在年轻成年小鼠 HSC 中未被检测到，直到被强制进入细胞周期。此外，通过整合蛋白质组学和 RNA 测序数据集，我们确定了一小部分基因在年轻成年小鼠 HSC 中存在明显的转录后抑制。总之，我们报告了年轻和老年小鼠 HSC 和祖细胞的蛋白质组覆盖范围，这对理解干细胞维持、龛位相互作用和命运决定的机制具有更广泛的意义。

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