Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development.
Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development.
复制标题
单细胞 RNA-Seq 分析揭示小鼠肝脏发育过程中的动态轨迹
DOI：
10.1186/s12864-017-4342-x
复制
发表时间：
2017-12-04
期刊：
影响因子：
4.4
通讯作者：
Han ZG
中科院分区：
文献类型：
--
作者：
Su X;Shi Y;Zou X;Lu ZN;Xie G;Yang JYH;Wu CC;Cui XF;He KY;Luo Q;Qu YL;Wang N;Wang L;Han ZG
胎儿肝干/祖细胞（LSPCs）的分化和成熟轨迹在单细胞分辨率下尚未完全了解，并且对有限生物标志物的先验知识可能会限制轨迹跟踪。结果采用无标记单细胞RNA-Seq技术，对小鼠肝脏发育过程中从胚胎第11.5天至出生后2.5天的7个阶段随机选取的507个细胞和出生后3.25天小鼠肝脏中提取的52个epcam阳性胆管细胞进行了全面的转录谱分析。通过无标记转录组分析鉴定发育中的小鼠肝脏中的LSPCs。LSPCs单细胞分辨率动态发育轨迹通过转录因子和信号通路表现出连续但离散的遗传控制。与其他后期LSPCs相比，胆管细胞的基因表达谱更接近胚胎第11.5天，表明LSPCs处于命运决定阶段。我们的无标记方法也允许系统评估和预测lspc的分离生物标志物。结论sour数据不仅为LSPCs自我更新、分化和成熟的命运决定和转录调控提供了宝贵的资源，而且为研究LSPCs的自我更新、分化和成熟提供了新的思路。
BackgroundThe differentiation and maturation trajectories of fetal liver stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution, and a priori knowledge of limited biomarkers could restrict trajectory tracking.ResultsWe employed marker-free single-cell RNA-Seq to characterize comprehensive transcriptional profiles of 507 cells randomly selected from seven stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver development, and also 52 Epcam-positive cholangiocytes from postnatal day 3.25 mouse livers. LSPCs in developing mouse livers were identified via marker-free transcriptomic profiling. Single-cell resolution dynamic developmental trajectories of LSPCs exhibited contiguous but discrete genetic control through transcription factors and signaling pathways. The gene expression profiles of cholangiocytes were more close to that of embryonic day 11.5 rather than other later staged LSPCs, cuing the fate decision stage of LSPCs. Our marker-free approach also allows systematic assessment and prediction of isolation biomarkers for LSPCs.ConclusionsOur data provide not only a valuable resource but also novel insights into the fate decision and transcriptional control of self-renewal, differentiation and maturation of LSPCs.
登录
查看更多内容
影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
影响因子：
13.5
作者：
Dianat, Noushin;Dubois-Pot-Schneider, Helene;Steichen, Clara;Desterke, Christophe;Leclerc, Philippe;Raveux, Aurelien;Combettes, Laurent;Weber, Anne;Corlu, Anne;Dubart-Kupperschmitt, Anne
通讯作者：
Dubart-Kupperschmitt, Anne
连续的 EMT-MET 机制驱动人胚胎干细胞向肝细胞分化。
影响因子：
16.6
作者：
Li Q;Hutchins AP;Chen Y;Li S;Shan Y;Liao B;Zheng D;Shi X;Li Y;Chan WY;Pan G;Wei S;Shu X;Pei D
通讯作者：
Pei D
影响因子：
4.8
作者：
Buglino, John A.;Resh, Marilyn D.
通讯作者：
Resh, Marilyn D.
影响因子：
29.4
作者：
Kamiya, Akihide;Kakinuma, Sei;Nakauchi, Hiromitsu
通讯作者：
Nakauchi, Hiromitsu