胚胎中的造血干细胞

造血干细胞前体中的Notch信号转导模型

　　两个独立的研究小组在新的研究中，演示了体节(沿胚胎前-后轴心形成的由中胚层细胞构成的成对的聚集体)在脊椎动物发育期间在造血干细胞(HSCs)的生成中所起作用。相关文章发表于2014年8月13日的《Nature》杂志上。

　　本期Nature上发表的两篇论文，演示了体节(沿胚胎前-后轴心形成的由中胚层细胞构成的成对的聚集体)在脊椎动物发育期间在造血干细胞(HSCs)的生成中所起作用。

　　Phong Dang Nguyen等人识别出一个以前不知道的体节腔室，被称为“endotome”，它通过提供内皮祖细胞来帮助胚胎背主动脉的形成。“endotome”的形成是由meox1的活性调控的，后者是含“同源盒”(homeobox)的一个转录因子。

　　Isao Kobayashi 等人报告，HSCs的前体在它们的胚胎迁移过程中与体节直接接触，这种相互作用是接收必要的Notch信号所需的。他们识别出调控这种接触的两个粘附分子：由HSC 前体表达的Jam1a和由体节表达的Jam2a。(来源：生物帮)

　　原文摘要：

Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1

Phong Dang Nguyen, Georgina Elizabeth Hollway, Carmen Sonntag, Lee Barry Miles,Thomas Edward Hall, Silke Berger, Kristine Joy Fernandez, David Baruch Gurevich,Nicholas James Cole, Sara Alaei, Mirana Ramialison, Robert Lyndsay Sutherland, Jose Maria Polo, Graham John Lieschke & Peter David Currie

　　Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events. Previous studies have identified that signalling relayed from adjacent somites coordinates HSC induction, but the nature of this signal has remained elusive. Here we reveal that somite specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the zebrafish somite that we have defined as the endotome. Endothelial cells of the endotome are specified within the nascent somite by the activity of the homeobox gene meox1. Specified endotomal cells consequently migrate and colonize the DA, wher they induce HSC formation through the deployment of chemokine signalling activated in these cells during endotome formation. Loss of meox1 activity expands the endotome at the expense of a second somitic cell type, the muscle precursors of the dermomyotomal equivalent in zebrafish, the external cell layer. The resulting increase in endotome-derived cells that migrate to colonize the DA generates a dramatic increase in chemokine-dependent HSC induction. This study reveals the molecular basis for a novel somite lineage restriction mechanism and defines a new paradigm in induction of definitive HSCs.

Jam1a–Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling

Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim, Claire Pouget, Naonobu Fujita,Toshio Suda & David Traver

　　Notch signalling plays a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development and requires intimate contact between signal-emitting and signal-receiving cells, although little is known regarding when, wher and how these intercellular events occur. We previously reported that the somitic Notch ligands, Dlc and Dld, are essential for HSC specification. It has remained unclear, however, how these somitic requirements are connected to the later emergence of HSCs from the dorsal aorta. Here we show in zebrafish that Notch signalling establishes HSC fate as their shared vascular precursors migrate across the ventral face of the somite and that junctional adhesion molecules (JAMs) mediate this required Notch signal transduction. HSC precursors express jam1a (also known as f11r) and migrate axially across the ventral somite, wher Jam2a and the Notch ligands Dlc and Dld are expressed. Despite no alteration in the expression of Notch ligand or receptor genes, loss of function of jam1a led to loss of Notch signalling and loss of HSCs. Enforced activation of Notch in shared vascular precursors rescued HSCs in jam1a or jam2a deficient embryos. Together, these results indicate that Jam1a–Jam2a interactions facilitate the transduction of requisite Notch signals from the somite to the precursors of HSCs, and that these events occur well before formation of the dorsal aorta.