Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors.
Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors.
复制标题
DOI：
10.1038/s41467-018-06442-4
复制
发表时间：
2018-10-05
影响因子：
16.6
通讯作者：
Laurenti E
中科院分区：
文献类型：
--
作者：
Belluschi S;Calderbank EF;Ciaurro V;Pijuan-Sala B;Santoro A;Mende N;Diamanti E;Sham KYC;Wang X;Lau WWY;Jawaid W;Göttgens B;Laurenti E
了解多能性在哪里以及如何丧失对于了解血液形成是如何控制的至关重要。目前认为，血液谱系特化发生在多能造血干细胞（HSC）的下游。在这里，我们表明，在人类中，第一谱系限制事件发生在CD 19 − CD 34 + CD 38 − CD 45 RA − CD 49 f + CD 90+（49 f+）HSC区室中，以产生没有红系分化能力的骨髓淋巴定向细胞。在单细胞分辨率下，我们观察到49 f+区室的连续但极化的组织，其中转录程序和谱系潜力沿着CLEC 9 A和CD 34的相反细胞表面表达的梯度沿着逐渐变化。CLEC 9AhiCD 34 lo细胞含有具有缓慢静止退出动力学的长期再增殖多能HSC，而CLEC 9AloCD 34 hi细胞限于骨髓淋巴样分化，并显示不频繁但持久的再增殖能力。因此，我们建议，人类造血干细胞逐渐过渡到一个离散的淋巴启动状态，不同的淋巴启动多能祖细胞，代表最早进入淋巴承诺点。人类血细胞都是从造血干细胞（HSC）发育而来的，造血干细胞被认为是多能的。在这里，作者使用单细胞RNA-seq和功能测定表明，红细胞潜能的丧失和对骨髓淋巴谱系的承诺发生在迄今为止最纯的HSC区室中。
Capturing where and how multipotency is lost is crucial to understand how blood formation is controlled. Blood lineage specification is currently thought to occur downstream of multipotent haematopoietic stem cells (HSC). Here we show that, in human, the first lineage restriction events occur within the CD19−CD34+CD38−CD45RA−CD49f+CD90+ (49f+) HSC compartment to generate myelo-lymphoid committed cells with no erythroid differentiation capacity. At single-cell resolution, we observe a continuous but polarised organisation of the 49f+ compartment, where transcriptional programmes and lineage potential progressively change along a gradient of opposing cell surface expression of CLEC9A and CD34. CLEC9AhiCD34lo cells contain long-term repopulating multipotent HSCs with slow quiescence exit kinetics, whereas CLEC9AloCD34hi cells are restricted to myelo-lymphoid differentiation and display infrequent but durable repopulation capacity. We thus propose that human HSCs gradually transition to a discrete lymphoid-primed state, distinct from lymphoid-primed multipotent progenitors, representing the earliest entry point into lymphoid commitment. Human blood cells all develop from haematopoietic stem cells (HSCs), classically thought to be multipotent. Here the authors show, using single-cell RNA-seq and functional assays, that loss of erythroid potential and commitment to the myelo-lymphoid lineage occurs within the purest HSC compartment to date.
登录
查看更多内容
影响因子：
30.5
作者：
Laurenti E;Doulatov S;Zandi S;Plumb I;Chen J;April C;Fan JB;Dick JE
通讯作者：
Dick JE
DOI：
10.1084/jem.20110447
发表时间：
2011-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kataoka K;Sato T;Yoshimi A;Goyama S;Tsuruta T;Kobayashi H;Shimabe M;Arai S;Nakagawa M;Imai Y;Kumano K;Kumagai K;Kubota N;Kadowaki T;Kurokawa M
通讯作者：
Kurokawa M
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
DOI：
10.1126/science.1251033
发表时间：
2014-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen L;Kostadima M;Martens JHA;Canu G;Garcia SP;Turro E;Downes K;Macaulay IC;Bielczyk-Maczynska E;Coe S;Farrow S;Poudel P;Burden F;Jansen SBG;Astle WJ;Attwood A;Bariana T;de Bono B;Breschi A;Chambers JC;Consortium B;Choudry FA;Clarke L;Coupland P;van der Ent M;Erber WN;Jansen JH;Favier R;Fenech ME;Foad N;Freson K;van Geet C;Gomez K;Guigo R;Hampshire D;Kelly AM;Kerstens HHD;Kooner JS;Laffan M;Lentaigne C;Labalette C;Martin T;Meacham S;Mumford A;Nürnberg S;Palumbo E;van der Reijden BA;Richardson D;Sammut SJ;Slodkowicz G;Tamuri AU;Vasquez L;Voss K;Watt S;Westbury S;Flicek P;Loos R;Goldman N;Bertone P;Read RJ;Richardson S;Cvejic A;Soranzo N;Ouwehand WH;Stunnenberg HG;Frontini M;Rendon A
通讯作者：
Rendon A
影响因子：
23.9
作者：
Dykstra, Brad;Kent, David;Eaves, Connie
通讯作者：
Eaves, Connie