nature：中国科学家在干细胞领域的最新成果
本文系细胞培养俱乐部整理翻译
作者：阿紫
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感谢周剑锋老师的资讯分享
2016年5月19日凌晨，《自然》在线发表了军事医学科学院刘兵、北大汤富酬、军事医学科学院血研所袁卫平课题组等人在造血干细胞领域的合作研究文章。这是中国人又一次在国际学术期刊发表的关于干细胞研究的文章，热烈祝贺。
文章摘要：
Haematopoietic stem cells (HSCs) are derived early from embryonic precursors, such as haemogenic endothelial cells and pre-haematopoietic stem cells (pre-HSCs), the molecular identity of which still remains elusive. Here we use potent surface markers to capture the nascent pre-HSCs at high purity, as rigorously validated by single-cell-initiated serial transplantation. Then we apply single-cell RNA sequencing to analyse endothelial cells, CD45− and CD45+ pre-HSCs in the aorta–gonad–mesonephros region, and HSCs in fetal liver. Pre-HSCs show unique features in transcriptional machinery, arterial signature, metabolism state, signalling pathway, and transcription factor network. Functionally, activation of mechanistic targets of rapamycin (mTOR) is shown to be indispensable for the emergence of HSCs but not haematopoietic progenitors. Transcriptome data-based functional analysis reveals remarkable heterogeneity in cell-cycle status of pre-HSCs. Finally, the core molecular signature of pre-HSCs is identified. Collectively, our work paves the way for dissection of complex molecular mechanisms regulating stepwise generation of HSCs in vivo, informing future efforts to engineer HSCs for clinical applications.
造血干细胞(hsc)早期来自胚胎前体,如相关的内皮细胞和造血干细胞前体细胞(pre-HSCs)，但是这些细胞的分子标记仍然难以捉摸。这里我们使用强有力的表面标记来捕获的新生高纯度pre-HSCs，作为严格验证的单细胞启动连续移植。然后我们应用单细胞RNA测序分析内皮细胞、CD45−和CD45 + pre-HSCs 主动脉-性腺-中胚肾区域和胎儿肝脏的造血干细胞。Pre-HSCs在转录结构、动脉信号、代谢状态、信号通路、转录因子网络显示独特的特性。功能地激活机用雷帕霉素(mTOR)功能地激活证明是造血干细胞不可或缺的，但不认为是造血祖细胞。转录组数据的功能分析显示显著的异质性pre-HSCs细胞循环状态。最后，pre-HSCs的核心分子标记确认。总的来说,我们的工作为体内造血干细胞逐步的产生分子机理奠定了基础，为工程化造血干细胞的临床应用指明了方向。
文章相关结果：
Figure 1 | Identification of T1 pre-HSCs at single-cell resolution.
Figure 2 | Enhanced enrichment of T2 pre-HSCs by single-cell RNA-seq.
Figure 3 | Global gene expression dynamics during HSC formation.
Figure 4 | Specific role of mTORC2 signalling during HSC formation.
Figure 5 | Signature genes and cell-cycle heterogeneity of pre-HSCs.
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