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New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology
Benjamin Patterson,Yoshiaki Tanaka,박인현 한국조직공학과 재생의학회 2017 조직공학과 재생의학 Vol.14 No.6
Recent advances in stem cell biology have dramatically increased the understanding of molecular and cellular mechanism of pluripotency and cell fate determination. Additionally, pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, arose as essential resources for disease modeling and cellular therapeutics. Despite these advancements, the epigenetic dysregulation in pluripotency such as the imprinting status, and X chromosome dosage compensation, and its consequences on future utility of PSCs yet remain unresolved. In this review, we will focus on the X chromosome regulation in human PSCs (hPSCs). We will introduce the previous findings in the dosage compensation process on mouse model, and make comparison with those of human systems. Particularly, the X chromosome activation status of human preimplantation embryos, and the regulation of the active X chromosome by human specific lincRNA, X Active Coating Transcript (XACT), will be discussed. We will also discuss the recent findings on higher order X chromosome architecture, and abnormal X chromosome status in hPSCs.
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Scalable production of tissue-like vascularized liver organoids from human PSCs
Harrison Sean P.,Siller Richard,Tanaka Yoshiaki,Chollet Maria Eugenia,de la Morena-Barrio María Eugenia,Xiang Yangfei,Patterson Benjamin,Andersen Elisabeth,Bravo-Pérez Carlos,Kempf Henning,Åsrud Kathr 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.
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