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Journal of Molecular Biology Apr 2016
Topics: Animals; Cell Differentiation; Humans; Signal Transduction; Stem Cells
PubMed: 26996938
DOI: 10.1016/j.jmb.2016.03.011 -
Open Biology Aug 2017Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are... (Review)
Review
Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells. We also highlight recent progress in molecular visualization that has allowed for the monitoring of Wnt signalling within the stem cell compartment and new approaches to recapitulate this niche signalling Indeed, new technologies that present Wnt in a localized manner and mimic the three-dimensional microenvironment of stem cells will advance our understanding of Wnt signalling in the stem cell niche. These advances will expand current horizons to exploit Wnt ligands in the rapidly evolving fields of tissue engineering and regenerative medicine.
Topics: Animals; Cell Differentiation; Cell Proliferation; Humans; Ligands; Stem Cell Niche; Stem Cells; Tissue Engineering; Wnt Signaling Pathway
PubMed: 28814649
DOI: 10.1098/rsob.170140 -
Seminars in Cell & Developmental Biology Apr 2016Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of... (Review)
Review
Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of metabolic pathways in the active control of vital cell functions. Case in point, the stem cell lifecycle--from maintenance and acquisition of stemness to lineage commitment and specification--is increasingly recognized as a metabolism-dependent process. Indeed, metabolic reprogramming is an early contributor to the orchestrated departure from or reacquisition of stemness. Recent advances in metabolomics have helped decipher the identity and dynamics of metabolic fluxes implicated in fueling cell fate choices by regulating the epigenetic and transcriptional identity of a cell. Metabolic cues, internal and/or external to the stem cell niche, facilitate progenitor pool restitution, long-term tissue renewal or ensure adoption of cytoprotective behavior. Convergence of energy metabolism with stem cell fate regulation opens a new avenue in understanding primordial developmental biology principles with future applications in regenerative medicine practice.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Energy Metabolism; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells
PubMed: 26868758
DOI: 10.1016/j.semcdb.2016.02.010 -
EMBO Reports Mar 2014Regenerative medicine aims to replace the lost or damaged cells in the human body through a new source of healthy transplanted cells or by endogenous repair. Although... (Review)
Review
Regenerative medicine aims to replace the lost or damaged cells in the human body through a new source of healthy transplanted cells or by endogenous repair. Although human embryonic stem cells were first thought to be the ideal source for cell therapy and tissue repair in humans, the discovery by Yamanaka and colleagues revolutionized the field. Almost any differentiated cell can be sent back in time to a pluripotency state by expressing the appropriate transcription factors. The process of somatic reprogramming using Yamanaka factors, many of which are oncogenes, offers a glimpse into how cancer stem cells may originate. In this review we discuss the similarities between tumor dedifferentiation and somatic cell reprogramming and how this may pose a risk to the application of this new technology in regenerative medicine.
Topics: Animals; Carcinogens; Cell Dedifferentiation; Cell Lineage; Cellular Reprogramming; Humans; Induced Pluripotent Stem Cells; Neoplastic Stem Cells
PubMed: 24531722
DOI: 10.1002/embr.201338254 -
Cellular and Molecular Life Sciences :... Feb 2014Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through... (Review)
Review
Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer.
Topics: Animals; Asymmetric Cell Division; Homeostasis; Humans; Neoplasms; Neural Stem Cells; Stem Cells
PubMed: 23771628
DOI: 10.1007/s00018-013-1386-1 -
Stem Cell Research & Therapy Jun 2022hPSC-derived endothelial and hematopoietic cells (ECs and HCs) are an interesting source of cells for tissue engineering. Despite their close spatial and temporal...
BACKGROUND
hPSC-derived endothelial and hematopoietic cells (ECs and HCs) are an interesting source of cells for tissue engineering. Despite their close spatial and temporal embryonic development, current hPSC differentiation protocols are specialized in only one of these lineages. In this study, we generated a hematoendothelial population that could be further differentiated in vitro to both lineages.
METHODS
Two hESCs and one hiPSC lines were differentiated into a hematoendothelial population, hPSC-ECs and blast colonies (hPSC-BCs) via CD144-embryoid bodies (hPSC-EBs). hPSC-ECs were characterized by endothelial colony-forming assay, LDL uptake assay, endothelial activation by TNF-α, nitric oxide detection and Matrigel-based tube formation. Hematopoietic colony-forming cell assay was performed from hPSC-BCs. Interestingly, we identified a hPSC-BC population characterized by the expression of both CD144 and CD45. hPSC-ECs and hPSC-BCs were analyzed by flow cytometry and RT-qPCR; in vivo experiments have been realized by ischemic tissue injury model on a mouse dorsal skinfold chamber and hematopoietic reconstitution in irradiated immunosuppressed mouse from hPSC-ECs and hPSC-EB-CD144, respectively. Transcriptomic analyses were performed to confirm the endothelial and hematopoietic identity of hESC-derived cell populations by comparing them against undifferentiated hESC, among each other's (e.g. hPSC-ECs vs. hPSC-EB-CD144) and against human embryonic liver (EL) endothelial, hematoendothelial and hematopoietic cell subpopulations.
RESULTS
A hematoendothelial population was obtained after 84 h of hPSC-EBs formation under serum-free conditions and isolated based on CD144 expression. Intrafemorally injection of hPSC-EB-CD144 contributed to the generation of CD45 human cells in immunodeficient mice suggesting the existence of hemogenic ECs within hPSC-EB-CD144. Endothelial differentiation of hPSC-EB-CD144 yields a population of > 95% functional ECs in vitro. hPSC-ECs derived through this protocol participated at the formation of new vessels in vivo in a mouse ischemia model. In vitro, hematopoietic differentiation of hPSC-EB-CD144 generated an intermediate population of > 90% CD43 hPSC-BCs capable to generate myeloid and erythroid colonies. Finally, the transcriptomic analyses confirmed the hematoendothelial, endothelial and hematopoietic identity of hPSC-EB-CD144, hPSC-ECs and hPSC-BCs, respectively, and the similarities between hPSC-BC-CD144CD45, a subpopulation of hPSC-BCs, and human EL hematopoietic stem cells/hematopoietic progenitors.
CONCLUSION
The present work reports a hPSC differentiation protocol into functional hematopoietic and endothelial cells through a hematoendothelial population. Both lineages were proven to display characteristics of physiological human cells, and therefore, they represent an interesting rapid source of cells for future cell therapy and tissue engineering.
Topics: Animals; Cell Differentiation; Embryoid Bodies; Endothelial Cells; Human Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Mice
PubMed: 35715824
DOI: 10.1186/s13287-022-02925-w -
Stem Cells Translational Medicine Mar 2022The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and... (Review)
Review
The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and tissues. Moreover, some blood vessels are home to essential stem-like cells, a classic example being the existence in the embryo of hemogenic endothelial cells at the origin of definitive hematopoiesis. In recent years, microvascular pericytes and adventitial perivascular cells were observed to include multi-lineage progenitor cells involved not only in organ turnover and regeneration but also in pathologic remodeling, including fibrosis and atherosclerosis. These perivascular mesodermal elements were identified as native forerunners of mesenchymal stem cells. We have presented in this brief review our current knowledge on vessel wall-associated tissue remodeling cells with respect to discriminating phenotypes, functional diversity in health and disease, and potential therapeutic interest.
Topics: Endothelial Cells; Humans; Mesenchymal Stem Cells; Pericytes; Peripheral Blood Stem Cells; Stem Cells
PubMed: 35641167
DOI: 10.1093/stcltm/szab001 -
Stem Cells (Dayton, Ohio) Nov 2015Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field... (Review)
Review
Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field of Developmental Biology and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a successful lineage-tracing experiment. In addition, I summarize and compare different methods for conducting lineage tracing and provide examples of how these strategies can be implemented to answer fundamental questions in development and regeneration. The advantages and limitations of each method are also discussed.
Topics: Animals; Cell Lineage; Embryonic Stem Cells; Fluorescent Dyes; Humans; Radiometric Dating; Staining and Labeling; Stem Cells
PubMed: 26284340
DOI: 10.1002/stem.2123 -
International Journal of Molecular... Oct 2015Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and... (Review)
Review
Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.
Topics: Aging; Animals; Cell Proliferation; Cellular Senescence; Humans; Regeneration; Stem Cells; Tissue Engineering
PubMed: 26512653
DOI: 10.3390/ijms161025392 -
Radiation Research Jul 2016Pluripotent stem cells (PSCs) hold great promise in regenerative medicine, disease modeling, functional genomics, toxicological studies and cell-based therapeutics due... (Review)
Review
Pluripotent stem cells (PSCs) hold great promise in regenerative medicine, disease modeling, functional genomics, toxicological studies and cell-based therapeutics due to their unique characteristics of self-renewal and pluripotency. Novel methods for generation of pluripotent stem cells and their differentiation to the specialized cell types such as neuronal cells, myocardial cells, hepatocytes and beta cells of the pancreas and many other cells of the body are constantly being refined. Pluripotent stem cell derived differentiated cells, including neuronal cells or cardiac cells, are ideal for stem cell transplantation as autologous or allogeneic cells from healthy donors due to their minimal risk of rejection. Radiation-induced DNA damage, ultraviolet light, genotoxic stress and other intrinsic and extrinsic factors triggers a series of biochemical reactions known as DNA damage response. To maintain genomic stability and avoid transmission of mutations into progenitors cells, stem cells have robust DNA damage response signaling, a contrast to somatic cells. Stem cell transplantation may protect against radiation-induced late effects. In particular, this review focuses on differential DNA damage response between stem cells and derived differentiated cells and the possible pathways that determine such differences.
Topics: Animals; DNA Damage; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 27332952
DOI: 10.1667/RR14417.1