Stem cell behavior at hypothermia: A review article

2020 ◽  
Vol 16 ◽  
Author(s):  
Sajjad Farashi ◽  
Esmaeel Sharifi
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Mild Hypothermia ◽  
Stem Cell Differentiation ◽  
Cellular Systems ◽  
Temperature Perturbation ◽  
Profound Hypothermia ◽  
Fundamental Factor ◽  
The Stability ◽  
Shock Proteins

Temperature is a fundamental factor that affects many functions and structural aspects of physiological systems. Despite its importance, little studies have performed so far for investigating the compartments and mechanisms engaged in the response of cellular systems to temperature perturbation. In this review, focusing on stem cells, we tried to perform a literature review for investigating the possible ways that temperature reduction [hypothermia] affects stem cell function and behavior. Besides, using the obtained results of this investigation, the possible mechanisms are proposed. The survey indicates that profound hypothermia enhances cell adhesion by increasing the stability of E-cadherins. Furthermore, mild hypothermia increases stem cell survival by reducing oxidative stress and prevents apoptosis via the overexpression of anti-apoptotic heat shock proteins. Mild-hypothermia also promotes cell proliferation by affecting gene expression in several ways. Even though it seems that hypothermia generally reduced stem cell differentiation, some inconsistencies are observed between obtained results from the literature. Based on the obtained results, mechanisms responsible for temperature effect of hypothermia in profound and mild ranges are given that might help researcher for real experiments.

scholarly journals Size-controlled human adipose-derived stem cell spheroids hybridized with single-segmented nanofibers and their effect on viability and stem cell differentiation

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Jinkyu Lee ◽  
Sangmin Lee ◽  
Sung Min Kim ◽  
Heungsoo Shin
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Average Length ◽  
Three Dimensional ◽  
Stem Cell Differentiation ◽  
Cell Spheroids ◽  
Significant Difference ◽  
Vitro Analysis ◽  
Physical And Chemical

Abstract Background Fabrication of three-dimensional stem cell spheroids have been studied to improve stem cell function, but the hypoxic core and limited penetration of nutrients and signaling cues to the interior of the spheroid were challenges. The incorporation of polymers such as silica and gelatin in spheroids resulted in relatively relaxed assembly of composite spheroids, and enhancing transport of nutrient and biological gas. However, because of the low surface area between cells and since the polymers were heterogeneously distributed throughout the spheroid, these polymers cannot increase the cell to extracellular matrix interactions needed to support differentiation. Methods We developed the stem cell spheroids that incorporate poly(ι-lactic acid) single-segmented fibers synthesized by electrospinning and physical and chemical fragmentation. The proper mixing ratio was 2000 cells/μg fibers (average length of the fibers was 50 μm - 100 μm). The SFs were coated with polydopamine to increase cell binding affinity and to synthesize various-sized spheroids. The function of spheroids was investigated by in vitro analysis depending on their sizes. For statistical analysis, Graphpad Prism 5 software (San Diego, CA, USA) was used to perform one-way analysis of variance ANOVA with Tukey’s honest significant difference test and a Student’s t-test (for two variables) (P < 0.05). Results Spheroids of different sizes were created by modulating the amount of cells and fibers (0.063 mm2–0.322 mm2). The fibers in the spheroid were homogenously distributed and increased cell viability, while cell-only spheroids showed a loss of DNA contents, internal degradation, and many apoptotic signals. Furthermore, we investigated stemness and various functions of various-sized fiber-incorporated spheroids. In conclusion, the spheroid with the largest size showed the greatest release of angiogenic factors (released VEGF: 0.111 ± 0.004 pg/ng DNA), while the smallest size showed greater effects of osteogenic differentiation (mineralized calcium: 18.099 ± 0.271 ng/ng DNA). Conclusion The spheroids incorporating polydopamine coated single-segmented fibers showed enhanced viability regardless of sizes and increased their functionality by regulating the size of spheroids which may be used for various tissue reconstruction and therapeutic applications.

scholarly journals Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism in Drosophila

2018 ◽  
Author(s):  
Rebecca Obniski ◽  
Matthew Sieber ◽  
Allan C. Spradling
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Notch Signaling ◽  
Cell Function ◽  
Dietary Cholesterol ◽  
Adult Life ◽  
Notch Pathway ◽  
Stem Cell Differentiation ◽  
Nuclear Hormone Receptor ◽  
Dietary Lipids

SummaryTissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with developmental pathways. Using the Drosophila midgut as a model we found that during the first four days of adult life, dietary lipids including cholesterol, determine how many enteroendocrine (ee) cells differentiate and persist in the posterior midgut where lipids are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, and utilization, is required for sterol-mediated changes in ee number. Dietary cholesterol influences new intestinal epithelial cell differentiation from stem cells by altering the level and persistance of Notch signaling. Exogenous lipids modulate signaling by changing the stability of the Delta ligand and Notch intracellular domain and their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues such as the ovary, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in ee number in young animals contribute to a metabolic program adapted to the prevailing nutrient environment that persists after the diet changes. A low sterol diet also slows the proliferation of enteroendocrine tumors initiated by disruptions in the Notch pathway. These studies show that a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.

scholarly journals Clonal inactivation of telomerase promotes accelerated stem cell differentiation

2021 ◽  
Author(s):  
Kazuteru Hasegawa ◽  
Yang Zhao ◽  
Alina Garbuzov ◽  
M. Ryan Corces ◽  
Lu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Function ◽  
Stem Cell Differentiation ◽  
Lineage Tracing ◽  
Open Chromatin ◽  
Loss Of Function ◽  
Direct Role ◽  
A Genome

SummaryTelomerase is intimately associated with stem cells and upregulated in cancer, where it serves essential roles through its catalytic action in elongating telomeres, nucleoprotein caps that protect chromosome ends1. Overexpression of the telomerase reverse transcriptase (TERT) enhances cell proliferation through telomere-independent means, yet definitive evidence for such a direct role in stem cell function has yet to be revealed through loss-of-function studies. Here, we show that conditional deletion of TERT in spermatogonial stem cells (SSCs) markedly impairs competitive clone formation. Using lineage-tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that selective TERT-inactivation in SSCs causes accelerated stem cell differentiation thereby disrupting clone formation. This requirement for TERT in clone formation is bypassed by expression of a catalytically inactive TERT transgene and occurs independently of the canonical telomerase complex. TERT inactivation induces a genome-wide reduction in open chromatin evident in purified SSCs, but not in committed progenitor cells. Loss of TERT causes reduced activity of the MYC oncogene and transgenic expression of MYC in TERT-deleted SSCs efficiently rescues clone formation. These data reveal a required catalytic activity-independent role for TERT in preventing stem cell differentiation, forge a genetic link between TERT and MYC and suggest new means by which TERT may promote tumorigenesis.

scholarly journals Mitochondria define intestinal stem cell differentiation downstream of a FOXO/Notch axis

2019 ◽  
Author(s):  
M.C. Ludikhuize ◽  
M. Meerlo ◽  
M. Pages Gallego ◽  
M. Burgaya Julià ◽  
N.T.B. Nguyen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Cell Function ◽  
Mitochondrial Fission ◽  
Stem Cell Differentiation ◽  
Notch Signalling ◽  
Intestinal Stem Cell ◽  
Mitochondrial Activity ◽  
Foxo Transcription Factors

SummaryDifferential signalling of the WNT and Notch pathways regulates proliferation and differentiation of Lgr5+ crypt-based columnar cells (CBCs) into all cell lineages of the intestine. We have recently shown that high mitochondrial activity in CBCs is key in maintaining stem cell function. Interestingly, while high mitochondrial activity drives CBCs, it is reduced in the adjacent secretory Paneth cells (PCs). This observation implies that during differentiation towards PCs, CBCs undergo a metabolic rewiring involving downregulation of mitochondrial number and activity, through a hitherto unknown mechanism. Here we demonstrate, using intestinal organoids that FoxO transcription factors and Notch signalling functionally interact in determining CBC cell fate. In agreement with the organoid data, combined Foxo1 and 3 deletion in mice increases PC number in the intestine. Importantly, we show that FOXO and Notch signalling converge onto regulation of mitochondrial fission, which in turn provokes stem cell differentiation into the secretory types; Goblet cells and PCs. Finally, mapping intestinal stem cell differentiation based on pseudotime computation of scRNA-seq data further supports the role of FOXO, Notch and mitochondria in determining secretory differentiation. This shows that mitochondria is not only a discriminatory hallmark of CBCs and PCs, but that its status actively determines lineage commitment during differentiation. Together, our work describes a new signalling-metabolic axis in stem cell differentiation and highlights the importance of mitochondria in determining cell fate.

scholarly journals Defining Parameters Attributing to the Role of Osteomacs in Regulating Stem Cell Function and the Hematopoietic Niche

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2576-2576
Author(s):  
Safa F. Mohamad ◽  
Joydeep Ghosh ◽  
Andrea M. Gunawan ◽  
Rachel Blosser ◽  
Malgorzata Kamocka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Function ◽  
Single Cells ◽  
Stem Cell Differentiation ◽  
Cell Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic Niche ◽  
Hematopoietic Activity

Abstract Networking between hematopoietic stem cells (HSC) and cells of the hematopoietic niche is critical for the maintenance of stem cell renewal and function. HSC maintenance in the hematopoietic niche is considered to be the product of intimate interactions between cellular and soluble elements of the niche and stem cells. Among the cellular components of the niche participating in this function are a group of specialized bone-resident macrophages known as osteomacs (OM). Previously, we established the importance of osteoblasts (OB) in hematopoiesis and quite recently, we described the importance of OM and their interactions with OB and megakaryocytes (MK) in sustaining HSC function. We have also illustrated that CD166 is a critical functional marker of stem cell function and competence of the hematopoietic niche. Interestingly, immature OB which are CD166+ mediate the highest level of hematopoietic enhancing activity. We report here the importance of CD166 on calvarie-resident OM (identified as CD45+F4/80+ cells) and outline how these cells require cooperation from MK to increase CD166 expression and sustain HSC function. Bone resident-osteomacs, which are phenotypically similar but functionally different from bone marrow-derived macrophages, were collected by the enzymatic digestion of neonatal calvarial cells (NCC) or long bones of adult mice. Transplantation assays indicated that OM are relatively radioresistant and survive several weeks post lethal radiation. However, they eventually deplete and are replenished by progeny of donor HSC. To understand the importance of OM-OB-MK interactions in maintaining HSC function in the niche, we performed 3D cytometry on fixed and stained bone marrow sections that revealed intimate spatial interactions between OM, OB, MK and HSC. To assess changes in gene expression observed due to these interactions, we cultured NCC for 16hr in the absence or presence of MK prepared from fetal liver followed by sorting out OM from each group. These cells were then captured as single cells and sequenced to identify potential targets through which OM enhanced hematopoietic activity. Strikingly, several genes involved in the hematopoietic stem cell differentiation pathway including lmo2, fli1 and ikzf1 were upregulated in OM cultured in the presence of MK. Other genes that were upregulated were embigin and PF-4, both of which have been implicated in the maintenance of HSC function. Interestingly, OM express embigin, angiogenin and IL-18 mRNA similar to proximal osteolineage cells which we previously described as HSC regulators. To investigate changes at the translational level, we performed single cell proteomics using CyTOF. NCC were cultured for 2 days in the absence and presence of MK followed by staining for a panel of 29 surface and intracellular markers. Expression of markers such as CD166, embigin, mac-2 and STAT3 amongst others was elevated on OM cultured with MK compared to OM cultured without. These data informed our decision to focus our future investigations on CD166 and embigin. Next CD166+OM and CD166-OM were isolated by cell sorting and used in co-culture assays with OB to support the production of clonogenic cells in vitro. Only the CD166+ fraction of OM maintained hematopoietic activity similar to unsorted OM, implicating CD166 as one of the mediators of OM function. These results were validated using recombinant CD166 protein to substitute for OM function. Under these conditions, recombinant CD166 supported the hematopoietic enhancing activity of OB in the absence of OM. Recombinant Angiogenin and IL-18 were unable to augment the CD166-mediated support of hematopoiesis. Interestingly, CD166 knockout OM were unable to mediate the same hematopoietic enhancing activity observed with WT OM regardless of the presence or absence of MK in culture. In vivo transplantation studies to corroborate these findings have been initiated and are very early to yield meaningful conclusions. These data demonstrate that CD166 is one of the important mediators through which OM maintain HSC function. However, CD166-OM mediated HSC function is only maintained in conjunction with OB-MK interactions. Our data indicate the importance of crosstalk between OM, OB and MK which leads to the expression of novel mediators such as CD166 to support HSC function. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Gadd45 Family As Mediators of Hematopoietic Stem Cell Differentiation - from Genotoxic Stress to Cytokine-Induced Differentiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1188-1188
Author(s):  
Susanne Wingert ◽  
Frederic B Thalheimer ◽  
Nadine Haetscher ◽  
Maike Rehage ◽  
Hubert Serve ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Genotoxic Stress ◽  
Time Lapse ◽  
Cellular Systems ◽  
Hematopoietic Stem ◽  
Time Lapse Microscopy ◽  
Differentiation Induction

Abstract The growth arrest and DNA-damage-inducible 45 (Gadd45) protein family is encoded by three genes, Gadd45a, b and g. All members of the family are early responders of cellular stress with tumor-suppressive function. In leukemia, the Gadd45 genes are often epigenetically silenced. Lately, we identified the GADD45 Gamma as the molecular link of differentiation-promoting cytokines to induce differentiation in HSCs (1). Here, we unraveled the function of the genotoxic stress-induced family member GADD45 Alpha (GADD45A) in hematopoiesis. GADD45A has been implicated in cell cycle control, cell death and senescence, as well as in DNA damage repair. In general, GADD45A provides cellular stability by either arresting the cell cycle progression until DNA damage is repaired or, in cases of fatal damage, by inducing apoptosis. However, the function of GADD45A in hematopoiesis remains highly controversial. We revealed the changes in murine HSC fate control orchestrated by the expression of GADD45A at single cell resolution using time-lapse microscopy-based HSC tracking. In contrast to other cellular systems, GADD45A expression neither caused a cell cycle arrest nor an alteration in the decision between cell survival and apoptosis in HSCs. Strikingly, GADD45A strongly induced and accelerated the differentiation program in HSCs. Continuous tracking of individual HSCs and their progeny via time-lapse microscopy elucidated that once GADD45A was expressed, HSCs differentiate into committed progenitors within 29 h. GADD45A-expressing HSCs failed to long-term reconstitute the blood of recipients by inducing multi-lineage differentiation in vivo. The differentiation induction by GADD45A was transmitted by activating p38 MAPK signaling, and allowed the generation of megakaryocytic-erythroid, myeloid and lymphoid lineages. These data indicate that genotoxic stress-induced GADD45A expression in HSCs prevents their fatal transformation by directing them into differentiation and thereby clearing them from the system. As the differentiation induction is conserved throughout the GADD45 family our study establishes this cell fate as an HSC-specific DNA-damage escape mechanism. Comparative analyses of the three proteins will further dissect the induced mechanisms at the molecular level. (1) Thalheimer, F.B., Wingert, S., De Giacomo, P., Haetscher, N., Rehage, M., Brill, B., Theis, F.J., Hennighausen, L., Schroeder, T., Rieger, M.A. Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells. Stem Cell Reports 3(1):34-43. (2014) Disclosures No relevant conflicts of interest to declare.

The many faces of p38 mitogen-activated protein kinase in progenitor/stem cell differentiation

2012 ◽  
Vol 445 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Feride Oeztuerk-Winder ◽  
Juan-Jose Ventura
Keyword(s):  
Stem Cell ◽  
Protein Kinase ◽  
Progenitor Cells ◽  
Cell Function ◽  
Current Knowledge ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Stem Cell Regulation ◽  
Mitogen Activated Protein

Regulation of stem cells is essential for development and adult tissue homoeostasis. The proper control of stem cell self-renewal and differentiation maintains organ physiology, and disruption of such a balance results in disease. There are many mechanisms that have been established as stem cell regulators, such as Wnt or Notch signals. However, the intracellular mechanisms that mediate and integrate these signals are not well understood. A new intracellular pathway that has been reported to be involved in the regulation of many stem cell types is that of p38 MAPK (mitogen-activated protein kinase). In particular, p38α is essential for the proper differentiation of many haematopoietic, mesenchymal and epithelial stem/progenitor cells. Many reports have shown that disruption of this kinase pathway has pathological consequences in many organs. Understanding the extracellular cues and downstream targets of p38α in stem cell regulation may help to tackle some of the pathologies associated with improper differentiation and regulation of stem cell function. In the present review we present a vision of the current knowledge on the roles of the p38α signal as a regulator of stem/progenitor cells in different tissues in physiology and disease.

scholarly journals Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation

2021 ◽  
Vol 22 (13) ◽  
pp. 6686
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Renzo Pala ◽  
Maria Laura Cossu ◽  
Giorgio Carlo Ginesu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Low Grade ◽  
Mrna Levels ◽  
Tnf Α ◽  
Shock Proteins

Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.

scholarly journals Transcription Factor DLX5 Promotes Hair Follicle Stem Cell Differentiation by Regulating the c-MYC/microRNA-29c-3p/NSD1 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Bojie Lin ◽  
Jiangying Zhu ◽  
Guoqian Yin ◽  
Mingde Liao ◽  
Guanyu Lin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Hair Follicle ◽  
Promoter Region ◽  
Cell Function ◽  
Adult Stem Cell ◽  
Stem Cell Differentiation ◽  
Model Systems ◽  
Hair Follicle Stem Cell

IntroductionAdult stem cell function has been one of the most intensively explored areas of biological and biomedical research, with hair follicle stem cells serving as one of the best model systems. This study explored the role of the transcription factor DLX5 in regulating hair follicle stem cell (HFSC) differentiation.MethodsHFSCs were isolated, characterized, and assessed for their expression of DLX5, c-MYC, NSD1, and miR-29c-3p using RT-qPCR, Western blot analysis, or immunofluorescence. Next, the ability of HFSCs to proliferate as well as differentiate into either sebaceous gland cells or epidermal cells was determined. The binding of DLX5 to the c-MYC promoter region, the binding of c-MYC to the miR-29c-3p promoter region, and the binding of miR-29c-3p to the 3′-UTR of NSD1 mRNA were verified by luciferase activity assay and ChIP experiments.ResultsDLX5 was highly expressed in differentiated HFSCs. DLX5 transcriptionally activated c-MYC expression to induce HFSC differentiation. c-MYC was able to bind the miR-29c-3p promoter and thus suppressed its expression. Without miR-29c-3p mediated suppression, NSD1 was then able to promote HFSC differentiation. These in vitro experiments suggested that DLX5 could promote HFSC differentiation via the regulation of the c-MYC/miR-29c-3p/NSD1 axis.DiscussionThis study demonstrates that DLX5 promotes HFSC differentiation by modulating the c-MYC/miR-29c-3p/NSD1 axis and identifies a new mechanism regulating HFSC differentiation.

scholarly journals The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation

Blood ◽  
2012 ◽  
Vol 119 (6) ◽  
pp. 1370-1379 ◽  
Author(s):  
Anastasia Nijnik ◽  
Simon Clare ◽  
Christine Hale ◽  
Claire Raisen ◽  
Rebecca E. McIntyre ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
P53 Protein ◽  
Critical Role ◽  
Chromatin Modification ◽  
Stem Cell Differentiation ◽  
Histone H2a ◽  
Mammalian Development ◽  
Hematopoietic Progenitors ◽  
Erythroid Progenitor

Abstract Stem cell differentiation and lineage specification depend on coordinated programs of gene expression, but our knowledge of the chromatin-modifying factors regulating these events remains incomplete. Ubiquitination of histone H2A (H2A-K119u) is a common chromatin modification associated with gene silencing, and controlled by the ubiquitin-ligase polycomb repressor complex 1 (PRC1) and H2A-deubiquitinating enzymes (H2A-DUBs). The roles of H2A-DUBs in mammalian development, stem cells, and hematopoiesis have not been addressed. Here we characterized an H2A-DUB targeted mouse line Mysm1tm1a/tm1a and demonstrated defects in BM hematopoiesis, resulting in lymphopenia, anemia, and thrombocytosis. Development of lymphocytes was impaired from the earliest stages of their differentiation, and there was also a depletion of erythroid cells and a defect in erythroid progenitor function. These phenotypes resulted from a cell-intrinsic requirement for Mysm1 in the BM. Importantly, Mysm1tm1a/tm1a HSCs were functionally impaired, and this was associated with elevated levels of reactive oxygen species, γH2AX DNA damage marker, and p53 protein in the hematopoietic progenitors. Overall, these data establish a role for Mysm1 in the maintenance of BM stem cell function, in the control of oxidative stress and genetic stability in hematopoietic progenitors, and in the development of lymphoid and erythroid lineages.

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