Cell Regeneration最新文献

Organoids have attracted great interest for disease modelling, drug discovery and development, and tissue growth and homeostasis investigations. However, lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications. "Human intestinal organoids" is the first guideline on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods, inspection rules for human intestinal organoids, which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids. It was originally released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.

High-throughput phenotypic screening is a cornerstone of drug development and the main technical approach for stem cell research. However, simultaneous detection of activated core factors responsible for cell fate determination and accurate assessment of directional cell transition are difficult using conventional screening methods that focus on changes in only a few biomarkers. The PHDs-seq (Probe Hybridization based Drug screening by sequencing) platform was developed to evaluate compound function based on their transcriptional effects in a wide range of signature biomarkers. In this proof-of-concept demonstration, several sets of markers related to cell fate determination were profiled in adipocyte reprogramming from dermal fibroblasts. After validating the accuracy, sensitivity and reproducibility of PHDs-seq data in molecular and cellular assays, a panel of 128 signalling-related compounds was screened for the ability to induce reprogramming of keloid fibroblasts (KF) into adipocytes. Notably, the potent ATP-competitive VEGFR/PDGFR inhibitor compound, ABT869, was found to promote the transition from fibroblasts to adipocytes. This study highlights the power and accuracy of the PHDs-seq platform for high-throughput drug screening in stem cell research, and supports its use in basic explorations of the molecular mechanisms underlying disease development.

Activation of regeneration upon tissue damages requires the activation of many developmental genes responsible for cell proliferation, migration, differentiation, and tissue patterning. Ample evidence revealed that the regulation of chromatin organization functions as a crucial mechanism for establishing and maintaining cellular identity through precise control of gene transcription. The alteration of chromatin organization can lead to changes in chromatin accessibility and/or enhancer-promoter interactions. Like embryogenesis, each stage of tissue regeneration is accompanied by dynamic changes of chromatin organization in regeneration-responsive cells. In the past decade, many studies have been conducted to investigate the contribution of chromatin organization during regeneration in various tissues, organs, and organisms. A collection of chromatin regulators were demonstrated to play critical roles in regeneration. In this review, we will summarize the progress in the understanding of chromatin organization during regeneration in different research organisms and discuss potential common mechanisms responsible for the activation of regeneration response program.

The regeneration capacity after an injury is critical to the survival of living organisms. In animals, regeneration ability can be classified into five primary types: cellular, tissue, organ, structure, and whole-body regeneration. Multiple organelles and signaling pathways are involved in the processes of initiation, progression, and completion of regeneration. Mitochondria, as intracellular signaling platforms of pleiotropic functions in animals, have recently gained attention in animal regeneration. However, most studies to date have focused on cellular and tissue regeneration. A mechanistic understanding of the mitochondrial role in large-scale regeneration is unclear. Here, we reviewed findings related to mitochondrial involvement in animal regeneration. We outlined the evidence of mitochondrial dynamics across different animal models. Moreover, we emphasized the impact of defects and perturbation in mitochondria resulting in regeneration failure. Ultimately, we discussed the regulation of aging by mitochondria in animal regeneration and recommended this for future study. We hope this review will serve as a means to advocate for more mechanistic studies of mitochondria related to animal regeneration on different scales.

Adipose tissues are essential for actively regulating systemic energy balance, glucose homeostasis, immune responses, reproduction, and longevity. Adipocytes maintain dynamic metabolic needs and possess heterogeneity in energy storage and supply. Overexpansion of adipose tissue, especially the visceral type, is a high risk for diabetes and other metabolic diseases. Changes in adipocytes, hypertrophy or hyperplasia, contribute to the remodeling of obese adipose tissues, accompanied by abundant immune cell accumulation, decreased angiogenesis, and aberrant extracellular matrix deposition. The process and mechanism of adipogenesis are well known, however, adipose precursors and their fate decision are only being defined with recent information available to decipher how adipose tissues generate, maintain, and remodel. Here, we discuss the key findings that identify adipose precursors phenotypically, with special emphasis on the intrinsic and extrinsic signals in instructing and regulating the fate of adipose precursors under pathophysiological conditions. We hope that the information in this review lead to novel therapeutic strategies to combat obesity and related metabolic diseases.

Hematopoietic stem cells (HSCs) are critical for the treatment of a variety of hematological diseases. However, the low number of HSCs lead to the clinical application difficult. To gain more functional human HSCs ex vivo, Sakurai et al. established a recombinant-cytokine-free and albumin-free culture system, i.e. PCL-PVAc-PEG-based culture, in combination with 740Y-P, butyzamide and UM171, to improve the long-term expansion of human cord blood HSCs.

The lung is the most critical organ of the respiratory system supporting gas exchange. Constant interaction with the external environment makes the lung vulnerable to injury. Thus, a deeper understanding of cellular and molecular processes underlying lung development programs and evaluation of progenitor status within the lung is an essential part of lung regenerative medicine. In this review, we aim to discuss the current understanding of lung development process and regenerative capability. We highlight the advances brought by multi-omics approaches, single-cell transcriptome, in particular, that can help us further dissect the cellular player and molecular signaling underlying those processes.

Steatosis, as the early stage of nonalcoholic fatty acid disease (NAFLD), would progress into nonalcoholic steatohepatitis (NASH) and liver failure without intervention. Despite the development of animal models, there is still a lack of the human-relevant platform for steatosis modeling and drug & target discovery. Hendriks et al., reporting in Nature Biotechnology, leveraged human fetal liver organoids to recapitulate steatosis by introducing nutritional and genetic triggers. Using these engineered liver organoid-derived steatosis models, they screened drugs that alleviate steatosis, and mined common mechanism of effective compounds. Further, inspired by the results of drug screening, the arrayed CRISPR-LOF screening targeting 35 lipid metabolism genes was performed, and FADS2 was identified as a critical regulator of steatosis.

The difficulties of injured and degenerated neurons to regenerate neurites and regain functions are more significant than in other body tissues, making neurodegenerative and related diseases hard to cure. Uncovering the secrets of neural regeneration and how this process may be inhibited after injury will provide insights into novel management and potential treatments for these diseases. Caenorhabditis elegans and Drosophila melanogaster are two of the most widely used and well-established model organisms endowed with advantages in genetic manipulation and live imaging to explore this fundamental question about neural regeneration. Here, we review the classical models and techniques, and the involvement and cooperation of subcellular structures during neurite regeneration using these two organisms. Finally, we list several important open questions that we look forward to inspiring future research.