RNAseq anaylsis of three Islet-1+ Cardiac Stem Cell Clones derived from Neonatal Cardiac Tissue
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE254267 | GEO | 2026/01/28
REPOSITORIES: GEO
Dataset's files
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| GSE254267_Quantification_of_Islet-1+_CSC_Expression.xlsx | Xlsx |
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Project description:Multipotent adult resident cardiac stem cells (CSCs) originally were identified by the expression of c-kit, the stem cell factor receptor. However, in the adult myocardium c-kit alone distinguish CSCs from other c-kit-expressing cardiac cells because the adult heart contains a heterogeneous mixture of c-kitpos cells, mainly composed of mast and endothelial/progenitor cells. This heterogeneity of cardiac c-kitpos cells has not been considered in recent c-kit-expressing cell fate mapping publications, which have equated the contribution of the whole heterogeneous c-kitpos population to cardiomyocyte generation in adulthood, which is minimal, to that of the CSCs, a result at odds with previous publications. To shed light on this issue, we have assessed the identity, abundancy and myogenic potential of true multipotent CSCs within the total c-kitpos cardiac cell cohort. Blood lineage-committed c-kitpos cells were removed by CD45 negative sorting to obtain a CD45negc-kitpos cell population (<10% of the total c-kitpos cells), which is enriched for cells that express c-kit at low levels and possess all properties of multipotent stem/progenitor cells in vitro. These characteristics are absent from the c-kitneg and the lineage-committed c-kitpos cardiac cells. Single Linnegc-kitpos cell-derived CSC clones, representing 1-2% of total c-kitpos cells, when instructed by TGF-b/Wnt molecules, acquire full transcriptome expression, sarcomere organization, spontaneous contraction and electrophysiological properties of differentiated cardiomyocytes. Significantly, clonogenic CSCs have a potent cardio-regenerative/repair capacity in vivo after acute myocardial infarction. CSC myogenic regenerative capacity is dependent on cardiomyocyte commitment through activation of the SMAD2 pathway. Such regeneration was not apparent when freshly-isolated total c-kitpos cardiac cells were administered. In conclusion, only a very small fraction of cardiac c-kitpos cells (~1-2%) have the characteristics of multipotent CSCs but these exhibit robust myogenic properties.
2017-07-25 | GSE95420 | GEO
Project description:Since the proliferative capacity of cardiomyocytes is extremely limited in the adult mammalian hearts, the irreversible loss of cardiomyocytes following cardiac injury markedly reduces cardiac function, leading to cardiac remodeling and heart failure. However, the early neonatal mice have a strong ability in cardiomyocyte proliferation and cardiac regeneration after heart damage such as apical resection. Besides of cardiomyocytes, non-myocytes in heart tissue also play important roles in the regeneration process. Previous studies showed that cardiac macrophages, regulatory T cells and CD4+ T cells are all involved in regulating the myocardial regeneration process. However, the roles of other cardiac immune cells in cardiac regeneration remains to be elucidated. B cells is a prominent immune cell in injured heart; here we discovered the indispensable function of cardiac B cells in improving cardiomyocyte proliferation and heart regeneration in neonatal mice.
2023-06-02 | GSE205115 | GEO
Project description:The importance of regenerative potential of cardiac stem/progenitor cells (CSCs) after acute myocardial infarction (AMI) has been emphasized in the last decade. Several studies have demonstrated that this cell population has a relevant role in myocardial repair, supported by the establishment of a paracrine cross-talk between CSCs and the injured tissue. However, the majority of current in vitro strategies to study these cells fails to include important modulators of CSC activity, such as the paracrine effect of cardiomyocytes (CMs) and the physicochemical changes occurring in tissue during Ischemia/Reperfusion (I/R) injury. In this work, we established the first human in vitro heterotypic model of myocardial I/R injury with human CSCs (hCSCs) and human induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs) using transwell inserts. hCSCs response to I/R was characterized using advanced whole proteomic mass spectrometry-based tools that allowed us to propose new pathways in hCSCs regenerative process, including: cell cycle regulation inhibition, proliferation through EGF signaling, gluthathione-mediated reactive oxygen species detoxification, and signaling through several paracrine growth factors. The model established in this work contributes with new insights regarding hCSC biology in response to AMI and provides an important tool to study and modulate molecular mechanisms involved in the regenerative potential of CSCs.
2019-02-18 | PXD008156 | Pride
Project description:Cardiac resident stem/progenitor cells are intensively studied as a potential therapeutic tool for cardiomyopathies. While surface marker expression and ability to generate cardiomyocytes have been characterized in some detail for several types of these progenitors, little is known on how their cardiac differentiation is regulated. Beta sarcoglycan null (bSG KO) mice are a model for limb girdle muscular dystrophy type 2E (LGMD2E), and are characterized by muscular dystrophy and progressive dilated cardiomyopathy. In the present study we isolated and characterized cardiac progenitors (mesoangioblasts) from the small vessels of neonatal hearts bSG KO mice and unexpectedly observed that they differentiate spontaneously into skeletal muscle fibers both in vitro and when transplanted in regenerating muscles and infarcted hearts. The micro array data showed that dystrophic cardiac progenitor and myogenic cells (C2C12) share similar gene expression profile. Keywords: Beta sarcoglycan null mice, muscular dystrophy, cardiac mesoangioblasts, myogenic differentiation Biological triplicates of cardiac wild-type and dystrophic mesoangioblasts isolated from different heart region (atrium, ventricle, aorta) were compared. C2C12 cells were used as positive control for myogenic differentiation.
2011-04-19 | E-GEOD-17774 | biostudies-arrayexpress
Project description:Senescence plays a key role in various physiological and pathological processes. We reported that injury-induced transient senescence correlates with heart regeneration, yet the multi-omics profile and molecular underpinnings of regenerative senescence remain obscure. Using proteomics and single-cell RNA-sequencing, here we report the regenerative senescence multi-omic signature in the adult mouse heart and establish its role in neonatal heart regeneration and Agrin-mediated cardiac repair in adult mice. We identified early growth response protein 1 (Egr1) as a regulator of regenerative senescence in both models. In the neonatal heart, Egr1 facilitates angiogenesis and cardiomyocyte proliferation. In adult hearts, Agrin-induced senescence and repair require Egr1, activated by the integrin/FAK-ERK/Akt1 axis in cardiac fibroblasts. We also identified cathepsins as injury-induced senescence-associated secretory phenotype (SASP) components that promote ECM degradation and potentially assist in reducing fibrosis. Altogether, we uncovered the molecular signature and functional benefits of regenerative senescence during heart regeneration, with Egr1 orchestrating the process.
2024-05-07 | GSE253383 | GEO
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
2014-12-20 | E-GEOD-64403 | biostudies-arrayexpress
Project description:Myxomas, the most common primary tumor of the heart, usually develop in the atria and consist of a myxoid matrix composed of an acid-mucopolysaccharide-rich stroma with polygonal stromal cells scattered throughout the matrix. These benign tumors, despite their rarity, are a research focus because of their clinical presentation and uncertain histogenesis. The objective of this study was to assess whether adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells and secrete the typical myxoid matrix. 23 collected tumors showed the typical histological features of cardiac atrial myxoma with polygonal cells positive for the myxoma tumor-cell marker, calretinin, dispersed in an abundant myxoid matrix. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of these c-kitpos cells were lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Some (<10%) of these c-kitpos/ CD45neg/CD31neg/ myxoma cells expressed also calretinin, representing myxoma stromal precursor cells. c-kitpos/CD45neg/CD31neg cardiac myxoma cells secrete in vitro chondroitin-6-sulfate and hyaluronic acid, composing the gelatinous matrix of cardiac myxoma in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. On the other hand, they exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to normal c-kitpos/CD45neg /CD31neg CSCs. Importantly, myxoma-derived CSCs seed human atrial myxoma in xenograft’s experiments in NOD/SCID mice. Thus, un-committed c-kitpos/CD45neg /CD31neg cells fulfill the criteria of myxoma stem cells in atrial myxoma. Myxomas appear to be the first CSC-related human cardiac disease.
2020-05-02 | E-MTAB-8642 | biostudies-arrayexpress
Project description:Myxomas, the most common primary tumor of the heart, usually develop in the atria and consist of a myxoid matrix composed of an acid-mucopolysaccharide-rich stroma with polygonal stromal cells scattered throughout the matrix. These benign tumors, despite their rarity, are a research focus because of their clinical presentation and uncertain histogenesis. The objective of this study was to assess whether adult cardiac stem/progenitor cells (CSCs) give rise to myxoma stromal cells and secrete the typical myxoid matrix. 23 collected tumors showed the typical histological features of cardiac atrial myxoma with polygonal cells positive for the myxoma tumor-cell marker, calretinin, dispersed in an abundant myxoid matrix. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of these c-kitpos cells were lineage-committed CD45pos/CD31pos cells. However, c-kitpos /CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Some (<10%) of these c-kitpos/ CD45neg/CD31neg/ myxoma cells expressed also calretinin, representing myxoma stromal precursor cells. c-kitpos/CD45neg/CD31neg cardiac myxoma cells secrete in vitro chondroitin-6-sulfate and hyaluronic acid, composing the gelatinous matrix of cardiac myxoma in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing and sphere forming. On the other hand, they exhibited an abortive cardiac differentiation potential with significant changes in their mRNA and microRNA transcriptome compared to normal c-kitpos/CD45neg /CD31neg CSCs. Importantly, myxoma-derived CSCs seed human atrial myxoma in xenograft’s experiments in NOD/SCID mice. Thus, un-committed c-kitpos/CD45neg /CD31neg cells fulfill the criteria of myxoma stem cells in atrial myxoma. Myxomas appear to be the first CSC-related human cardiac disease.
2020-04-01 | E-MTAB-8701 | biostudies-arrayexpress
Project description:In mammals, the neonatal heart regenerates within a short time after birth, but adults lack this ability. We have shown that metabolic reprogramming is critical for cardiomyocyte proliferation in the neonatal heart. Herein, we revealed that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. 4D label-free proteomics and Kla omics were performed in postnatal Day 1 (P1), 5 (P5), and 7 (P7) mouse hearts, 2297 Kla sites from 980 proteins were identified, and 1262 Kla sites from 409 proteins were quantified. Functional clustering analysis of proteins with altered Kla sites revealed that the proteins were mainly involved in metabolic processes. The Kla levels in several fatty acid oxidation-related proteins showed high expression at P5, while glycolysis and cell cycle-related proteins were sustainedly decreased from P1-P7. Furthermore, we verified the Kla levels of several differentially modified proteins, including ACAT1, ACADL, PKM and NPM1, by coimmunoprecipitation and Western blotting. Overall, we reported the first comprehensive Kla map in the neonatal mouse heart, which will aid in understanding the regulatory network of metabolic reprogramming and cardiac regeneration.
2024-07-02 | PXD039257 | Pride
Project description:Background: Following cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation. Methods: We studied the intergenerational influence of neonatal cardiac injury in the mouse. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult. Results: We show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy. Conclusions: The memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.
2024-11-08 | GSE254827 | GEO