同種骨髄移植後の新規免疫モニタリングシステムと免疫寛容メカニズムの解明

科学研究費助成事業 研究成果報告書：基盤研究(C)2015-2017課題番号 : 15K0949

Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells

Embryonic stem cells (ESCs) could potentially compensate for the lack of blood platelets available for use in transfusions. Here, we describe a new method for generating mouse ESC-derived platelets (ESPs) that can contribute to hemostasis in vivo. Flow cytometric sorting of cells from embryoid bodies on day 6 demonstrated that c-Kit+ integrin αIIb (αIIb)+ cells, but not CD31+ cells or vascular endothelial cadherin+ cells, are capable of megakaryopoiesis and the release of platelet-like structures by day 12. αIIbβ3-expressing ESPs exhibited ectodomain shedding of glycoprotein (GP)Ibα, GPV, and GPVI, but not αIIbβ3 or GPIbβ. ESPs showed impaired αIIbβ3 activation and integrin-mediated actin reorganization, critical events for normal platelet function. However, the administration of metalloproteinase inhibitors GM6001 or TAPI-1 during differentiation increased the expression of GPIbα, improving both thrombogenesis in vitro and posttransfusion recovery in vivo. Thus, the regulation of metalloproteinases in culture could be useful for obtaining high-quality, efficacious ESPs as an alternative platelet source for transfusions

SINC-seq: correlation of transient gene expressions between nucleus and cytoplasm reflects single-cell physiology

We report a microfluidic system that physically separates nuclear RNA (nucRNA) and cytoplasmic RNA (cytRNA) from a single cell and enables single-cell integrated nucRNA and cytRNA-sequencing (SINC-seq). SINC-seq constructs two individual RNA-seq libraries, nucRNA and cytRNA, per cell, quantifies gene expression in the subcellular compartments, and combines them to create novel single-cell RNA-seq data. Leveraging SINC-seq, we discover distinct natures of correlation among cytRNA and nucRNA that reflect the transient physiological state of single cells. These data provide unique insights into the regulatory network of messenger RNA from the nucleus toward the cytoplasm at the single-cell level

Compte rendu de « Desrosières, Alain (2014), Prouver et gouverner. Une analyse politique des statistiques publiques »

Prouver et gouverner étudie le rôle des institutions, des conventions et des enjeux normatifs dans la construction d’indicateurs quantitatifs. Desrosières pense qu’on ne peut étudier le développement scientifique des statistiques sans prendre en compte le développement institutionnel – en particulier le rôle de l’État – dans la constitution de cette discipline

The Road Map for Megakaryopoietic Lineage from Hematopoietic Stem/Progenitor Cells

Megakaryocytes (Mgks) are terminally differentiated blood cells specified to produce platelets, whereas hematopoietic stem cells (HSCs) are the most undifferentiated blood cells that retain multipotency to produce all kinds of blood cells. As such, these two cell types reside at the bottom and the top of the hematopoietic hierarchy, respectively. In spite of this distance, they share several important cell surface molecules as well as transcription factors.In the conventional step-wise differentiation model, HSCs gradually lose their self-renewal capacity and differentiate into multipotent progenitors (MPPs), which is the first branch point of myeloid and lymphoid lineage. In this model, common myeloid progenitors can differentiate into bipotent Mgk/erythroid progenitors (MEPs), and MEPs eventually differentiate into unipotent mature Mgks. However, it has been recently reported that a subpopulation within the HSC and MPP compartments demonstrates an Mgk-biased differentiation potential. These reports imply that revisions to the HSC-to-Mgk differentiation pathway should be discussed. In this review, we summarize recent findings about Mgk differentiation from HSCs and discuss future directions in this research field. Stem Cells Translational Medicine 2017;6:1661–166