Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels

The generation of induced pluripotent stem (iPS) cells is an important tool for regenerative medicine. However, the main restriction is the risk of tumor development. In this study we found that during the early stages of somatic cell reprogramming toward a pluripotent state, specific gene expression patterns are altered. Therefore, we developed a method to generate partial-iPS (PiPS) cells by transferring four reprogramming factors (OCT4, SOX2, KLF4, and c-MYC) to human fibroblasts for 4 d. PiPS cells did not form tumors in vivo and clearly displayed the potential to differentiate into endothelial cells (ECs) in response to defined media and culture conditions. To clarify the mechanism of PiPS cell differentiation into ECs, SET translocation (myeloid leukemia-associated) (SET) similar protein (SETSIP) was indentified to be induced during somatic cell reprogramming. Importantly, when PiPS cells were treated with VEGF, SETSIP was translocated to the cell nucleus, directly bound to the VE-cadherin promoter, increasing vascular endothelial-cadherin (VE-cadherin) expression levels and EC differentiation. Functionally, PiPS-ECs improved neovascularization and blood flow recovery in a hindlimb ischemic model. Furthermore, PiPS-ECs displayed good attachment, stabilization, patency, and typical vascular structure when seeded on decellularized vessel scaffolds. These findings indicate that reprogramming of fibroblasts into ECs via SETSIP and VEGF has a potential clinical application.

Smooth Muscle Cells Differentiated from Reprogrammed Embryonic Lung Fibroblasts Through DKK3 Signalling are Potent for Tissue Engineering of Vascular Grafts

Rationale: Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited.

Objective: We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state.

Methods and Results: We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft.

Conclusions: We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Le prince Yi Hou [i. e. Yi Un] et la princesse Masako après leur mariage : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60269

Un groupe de demoiselles d'honneur au mariage du prince Yi Hou [i. e. Yi Un] et la princesse Masako : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60268

新刻法家驚天雷Xin ke fa jia jing tian lei.Traité abrégé de droit.

Divisé en deux parties parallèles, imprimées l'une sur le haut de la page et l'autre sur le bas.2 livres.

王宜温和Wang yi wen he.Sur les devoirs d'un roi.

Sans nom d'auteur ni date.

初學玉玲瓏Chu xue yu ling long.Traité de composition.

Sur les divisions d'une pièce de wen zhang, avec exemples (thèmes des Quatre Livres). Par Xu Xuan Jing xian, de Tang ; préface de l'auteur (1750). Réédition de la salle Zhi yi (1835).4 livres.

新刊全像三寶 (sic) 太監西洋記通俗演義Xin kan quan xiang san bao tai jian xi yang ji tong su yan yi.Histoire du voyage en Occident de l'eunuque San bao, nouvelle édition illustrée.

Par Luo Mu tang (alias deng), surnom Er nan li ren, avec préface de l'auteur (1597). Récit des expéditions maritimes de Zheng He, surnom San bao tai jian († 1431). Portraits au début de chaque livre. Gravé au pavillon Bu yue.20 livres (100 hui).

新刊全像三寶 (sic) 太監西洋記通俗演義Xin kan quan xiang san bao tai jian xi yang ji tong su yan yi.Histoire du voyage en Occident de l'eunuque San bao, nouvelle édition illustrée.

Par Luo Mu tang (alias deng), surnom Er nan li ren, avec préface de l'auteur (1597). Récit des expéditions maritimes de Zheng He, surnom San bao tai jian († 1431). Portraits au début de chaque livre. Gravé au pavillon Bu yue.20 livres (100 hui).

新鐫全像武穆精忠傳Xin juan quan xiang wu mu jing zhong zhuan.Histoire de Yue Fei, nouvelle édition illustrée.

Par Li Chun fang, avec préface de l'auteur. Édition de Li Zhuo wu. Histoire de Yue Fei, de 1126 à 1155. Portraits des principaux personnages.8 livres.

靖海氛紀Jing hai fen ji.Pacification des pirates.

Par Yuan Yong lun, avec préfaces de 1830 par Su Ying heng et He Jing zhong. Ouvrage relatif aux pirateries exercées sur les côtes du Guang dong (1808-1809) consécutivement aux affaires d'Annam ; gravé à Canton en 1830. Suivi d'une annexe de 1835 par Zhou Shui sheng.2 livres.

六書實義Liu shu shi yi.Dialogue sur l'histoire de l'écriture.

Par Wen Gu zi, avec préface de 1720 et postface de 1721.

Liu shu shi yi.

Même ouvrage.

皇清勑封太孺人顯妣徐太宜人行實Huang qing chi feng tai ru ren xian bi xu tai yi ren xing shi.Vie de la dame Xu, née Xu (1600-1690).

Pièce rituelle composée par son fils Xu Yu.12 feuillets (incomplet).