Cell Regeneration最新文献

De novo organ regeneration is the process in which adventitious roots or shoots regenerate from detached or wounded organs. De novo organ regeneration can occur either in natural conditions, e.g. adventitious root regeneration from the wounded sites of detached leaves or stems, or in in-vitro tissue culture, e.g. organ regeneration from callus. In this review, we summarize recent advances in research on the molecular mechanism of de novo organ regeneration, focusing on the role of the WUSCHEL-RELATED HOMEOBOX11 (WOX11) gene in the model plant Arabidopsis thaliana. WOX11 is a direct target of the auxin signaling pathway, and it is expressed in, and regulates the establishment of, the founder cell during de novo root regeneration and callus formation. WOX11 activates the expression of its target genes to initiate root and callus primordia. Therefore, WOX11 links upstream auxin signaling to downstream cell fate transition during regeneration. We also discuss the role of WOX11 in diverse species and its evolution in plants.

Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and deteriorate a variety of hematopoietic malignancies such as leukemia. Myeloid cells and their precursors are difficult to capture in circulation, let alone observe them in real time. For decades, researchers had to face these difficulties, particularly in in-vivo studies. As a unique animal model, zebrafish possesses numerous advantages like body transparency and convenient genetic manipulation, which is very suitable in myelopoiesis research. Here we review current knowledge on the origin and regulation of myeloid development and how zebrafish models were applied in these studies.

Cell fate transition is a fascinating process involving complex dynamics of three-dimensional (3D) chromatin organization and phase separation, which play an essential role in cell fate decision by regulating gene expression. Phase separation is increasingly being considered a driving force of chromatin folding. In this review, we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure. In addition, we discuss current advances in understanding how phase separation contributes to physical and functional enhancer-promoter contacts. We highlight the functional roles of 3D chromatin organization and phase separation in cell fate transitions, and more explorations are required to study the regulatory relationship between 3D chromatin organization and phase separation. 3D chromatin organization (shown by Hi-C contact map) and phase separation are highly dynamic and play functional roles during early embryonic development, cell differentiation, somatic reprogramming, cell transdifferentiation and pathogenetic process. Phase separation can regulate 3D chromatin organization directly, but whether 3D chromatin organization regulates phase separation remains unclear.

Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full regeneration. Previous studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum (AP) cells and pedicle periosteum (PP) cells, respectively. As the cells resident in the AP and the PP possess stem cell attributes, both antler generation and regeneration are stem cell-based processes. However, the cell composition of each tissue type and molecular events underlying antler development remain poorly characterized. Here, we took the approach of single-cell RNA sequencing (scRNA-Seq) and identified eight cell types (mainly THY1⁺ cells, progenitor cells, and osteochondroblasts) and three core subclusters of the THY1⁺ cells (SC2, SC3, and SC4). Endothelial and mural cells each are heterogeneous at transcriptional level. It was the proliferation of progenitor, mural, and endothelial cells in the activated antler-lineage-specific tissues that drove the rapid formation of the antler. We detected the differences in the initial differentiation process between antler generation and regeneration using pseudotime trajectory analysis. These may be due to the difference in the degree of stemness of the AP-THY1⁺ and PP-THY1⁺ cells. We further found that androgen-RXFP2 axis may be involved in triggering initial antler full regeneration. Fully deciphering the cell composition for these antler tissue types will open up new avenues for elucidating the mechanism underlying antler full renewal in specific and regenerative medicine in general.

Skeletal muscle plays a critical role in human health. Muscle stem cells (MuSCs) serve as the major cell type contributing to muscle regeneration by directly differentiating to mature muscle cells. MuSCs usually remain quiescent with occasionally self-renewal and are activated to enter cell cycle for proliferation followed by differentiation upon muscle injury or under pathological conditions. The quiescence maintenance, activation, proliferation, and differentiation of MuSCs are tightly regulated. The MuSC cell-intrinsic regulatory network and the microenvironments work coordinately to orchestrate the fate transition of MuSCs. The heterogeneity of MuSCs further complicates the regulation of MuSCs. This review briefly summarizes the current progress on the heterogeneity of MuSCs and the microenvironments, epigenetic, and transcription regulations of MuSCs.

Mitochondria are organelles that serve numerous critical cellular functions, including energy production, Ca²⁺ homeostasis, redox signaling, and metabolism. These functions are intimately linked to mitochondrial morphology, which is highly dynamic and capable of rapid and transient changes to alter cellular functions in response to environmental cues and cellular demands. Mitochondrial morphology and activity are critical for various physiological processes, including wound healing. In mammals, wound healing is a complex process that requires coordinated function of multiple cell types and progresses in partially overlapping but distinct stages: hemostasis and inflammation, cell proliferation and migration, and tissue remodeling. The repair process at the single-cell level forms the basis for wound healing and regeneration in tissues. Recent findings reveal that mitochondria fulfill the intensive energy demand for wound repair and aid wound closure by cytoskeleton remodeling via morphological changes and mitochondrial reactive oxygen species (mtROS) signaling. In this review, we will mainly elucidate how wounding induces changes in mitochondrial morphology and activity and how these changes, in turn, contribute to cellular wound response and repair.

Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9⁺ progenitors by activating the Wnt/β-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.

Malignant glioma is a highly heterogeneous and invasive primary brain tumor characterized by high recurrence rates, resistance to combined therapy, and dismal prognosis. Glioma stem cells (GSCs) are likely responsible for tumor progression, resistance to therapy, recurrence, and poor prognosis owing to their high self-renewal and tumorigenic potential. As a family member of BMP signaling, bone morphogenetic protein4 (BMP4) has been reported to induce the differentiation of GSCs and neural stem cells (NSCs). However, the molecular mechanisms underlying the BMP4-mediated effects in these two cell types are unclear. In this study, we treated hGSCs and hNSCs with BMP4 and compared the phenotypic and transcriptional changes between these two cell types. Phenotypically, we found that the growth of hGSCs was greatly inhibited by BMP4, but the same treatment only increased the cell size of hNSCs. While the RNA sequencing results showed that BMP4 treatment evoked significantly transcriptional changes in both hGSCs and hNSCs, the profiles of differentially expressed genes were distinct between the two groups. A gene set that specifically targeted the proliferation and differentiation of hGSCs but not hNSCs was enriched and then validated in hGSC culture. Our results suggested that hGSCs and hNSCs responded differently to BMP4 stimulation. Understanding and investigating different responses between hGSCs and hNSCs will benefit finding partner factors working together with BMP4 to further suppress GSCs proliferation and stemness without disturbing NSCs.

Salamanders are excellent models for studying vertebrate brain regeneration, with the promise of developing novel therapies for human brain lesions. Yet the molecular and cellular mechanism of salamander brain regeneration remains largely elusive. The insight into the evolution of complex brain structures that lead to advanced functions in the mammalian brain is also inadequate. With high-resolution single-cell RNA sequencing and spatial transcriptomics, three recent studies have reported the differentiation paths of cells in the salamander telencephalon in the journal Science, bringing both old and new cell types into the focus and shedding light on vertebrate brain evolution, development, and regeneration.