scholarly journals Universal principles of lineage architecture and stem cell identity in renewing tissues

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Philip Greulich ◽  
Ben D. MacArthur ◽  
Cristina Parigini ◽  
Rubén J. Sánchez-García
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Feedback Regulation ◽  
Cell Types ◽  
Universal Principles ◽  
The People ◽  
Formal Framework ◽  
Cell Niche ◽  
Multicellular Organisms ◽  
The Relationship

ABSTRACT Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship between cell molecular ‘states’ and cell ‘types’, based on the topology of admissible cell state trajectories. We show that a self-renewing cell type – if defined as suggested by this framework – must reside at the top of any homeostatic renewing lineage hierarchy, and only there. This architecture arises as a natural consequence of homeostasis, and indeed is the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment, in accordance with the notion that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic characteristics. This article has an associated ‘The people behind the papers’ interview.

scholarly journals Universal principles of lineage architecture and stem cell identity in renewing tissues

2020 ◽  
Author(s):  
Philip Greulich ◽  
Ben D. MacArthur ◽  
Cristina Parigini ◽  
Rubén J. Sánchez-García
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Feedback Regulation ◽  
Cell Types ◽  
Universal Principles ◽  
Formal Framework ◽  
Cell Niche ◽  
Multicellular Organisms ◽  
The Relationship

Adult tissues in multicellular organisms typically contain a variety of stem, progenitor and differentiated cell types arranged in a lineage hierarchy that regulates healthy tissue turnover and repair. Lineage hierarchies in disparate tissues often exhibit common features, yet the general principles regulating their architecture are not known. Here, we provide a formal framework for understanding the relationship between cell molecular ‘states’ (patterns of gene, protein expression etc. in the cell) and cell ‘types’ that uses notions from network science to decompose the structure of cell state trajectories into functional units. Using this framework we show that many widely experimentally observed features of cell lineage architectures – including the fact that a single adult stem cell type always resides at the apex of a lineage hierarchy – arise as a natural consequence of homeostasis, and indeed are the only possible way that lineage architectures can be constructed to support homeostasis in renewing tissues. Furthermore, under suitable feedback regulation, for example from the stem cell niche, we show that the property of ‘stemness’ is entirely determined by the cell environment. Thus, we argue that stem cell identities are contextual and not determined by hard-wired, cell-intrinsic, characteristics.

scholarly journals Glioblastoma Distance From the Subventricular Neural Stem Cell Niche Does Not Correlate With Survival

2020 ◽  
Vol 10 ◽  
Author(s):  
Akshitkumar M. Mistry ◽  
Nishit Mummareddy ◽  
Sanjana Salwi ◽  
Larry T. Davis ◽  
Rebecca A. Ihrie
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Regression Model ◽  
Neural Stem Cell ◽  
Stem Cell Niche ◽  
Tumor Volume ◽  
Cox Regression ◽  
Cox Regression Model ◽  
Cell Niche ◽  
The Relationship

ObjectiveTo determine the relationship between survival and glioblastoma distance from the ventricular-subventricular neural stem cell niche (VSVZ).Methods502 pre-operative gadolinium-enhanced, T1-weighted MRIs with glioblastoma retrieved from an institutional dataset (n = 252) and The Cancer Imaging Atlas (n=250) were independently reviewed. The shortest distance from the tumor contrast enhancement to the nearest lateral ventricular wall, the location of the VSVZ, was measured (GBM-VSVZDist). The relationship of GBM-VSVZDist with the proportion of glioblastomas at each distance point and overall survival was explored with a Pearson’s correlation and Cox regression model, respectively, adjusting for the well-established glioblastoma prognosticators.Results244/502 glioblastomas had VSVZ contact. The proportion of non-VSVZ-contacting glioblastomas correlated inversely with GBM-VSVZDist (partial Pearson’s correlation adjusted for tumor volume R=-0.79, p=7.11x10-7). A fit of the Cox regression model adjusted for age at diagnosis, Karnofsky performance status score, post-operative treatment with temozolomide and/or radiotherapy, IDH1/2 mutation status, MGMT promoter methylation status, tumor volume, and extent of resection demonstrated a significantly decreased overall survival only when glioblastoma contacted the VSVZ. Overall survival did not correlate with GBM-VSVZDist.ConclusionsIn the two independent cohorts analyzed, glioblastomas at diagnosis were found in close proximity or in contact with the VSVZ with a proportion that decreased linearly with GBM-VSVZDist. Patient survival was only influenced by the presence or absence of a gadolinium-enhanced glioblastoma contact with the VSVZ. These results may guide analyses to test differential effectiveness of VSVZ radiation in VSVZ-contacting and non-contacting glioblastomas and/or inform patient selection criteria in clinical trials of glioblastoma radiation.

scholarly journals The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche

Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1857-1866 ◽  
Author(s):  
Ilaria Visigalli ◽  
Silvia Ungari ◽  
Sabata Martino ◽  
Hyejung Park ◽  
Martina Cesani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Disease Model ◽  
Cell Types ◽  
Hematopoietic Stem ◽  
Hematopoietic Stem Cell Niche ◽  
Intracellular Content ◽  
Cell Niche ◽  
And Function ◽  
Globoid Cell

Abstract The balance between survival and death in many cell types is regulated by small changes in the intracellular content of bioactive sphingolipids. Enzymes that either produce or degrade these sphingolipids control this equilibrium. The findings here described indicate that the lysosomal galactocerebrosidase (GALC) enzyme, defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell (HSPC) niche by contributing to the control of the intracellular content of key sphingolipids. Indeed, we show that both insufficient and supraphysiologic GALC activity—by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model—induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect HSPC survival and function and the functionality of the stem cell niche. Therefore, GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs.

scholarly journals Stem cell niche signals Wnt, Hedgehog, and Notch distinctively regulate Drosophila follicle precursor cell differentiation

2017 ◽  
Author(s):  
Wei Dai ◽  
Amy Peterson ◽  
Thomas Kenney ◽  
Denise J. Montell
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Wnt Signalling ◽  
Main Body ◽  
Cell Niche

AbstractAdult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. Signals within the stem cell niche maintain the undifferentiated state. However it is unclear whether or how niche signals might also coordinate fate decisions within the progenitor pool. Here we use quantitative microscopy to elucidate distinct roles for Wnt, Hedgehog (Hh), and Notch signalling in progenitor development in the Drosophila ovary. Follicle stem cells (FSCs) self-renew and produce precursors whose progeny adopt distinct polar, stalk, and main body cell fates. We show that a steep gradient of Wnt signalling maintains a multipotent state in proximally located progenitor cells by inhibiting expression of the cell fate determinant Eyes Absent (Eya). A shallower gradient of Hh signalling controls the proliferation to differentiation transition. The combination of Notch and Wnt signalling specifies polar cells. These findings reveal a mechanism by which multiple niche signals coordinate cell fate diversification of progenitor cells.

scholarly journals Space of Disse: a stem cell niche in the liver

2019 ◽  
Vol 401 (1) ◽  
pp. 81-95 ◽  
Author(s):  
Dieter Häussinger ◽  
Claus Kordes
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Stellate Cells ◽  
Cell Types ◽  
Trophic Factors ◽  
Perivascular Niche ◽  
Diseased Liver ◽  
Cell Niche ◽  
Space Of Disse ◽  
Parenchymal Cells

Abstract Recent evidence indicates that the plasticity of preexisting hepatocytes and bile duct cells is responsible for the appearance of intermediate progenitor cells capable of restoring liver mass after injury without the need of a stem cell compartment. However, mesenchymal stem cells (MSCs) exist in all organs and are associated with blood vessels which represent their perivascular stem cell niche. MSCs are multipotent and can differentiate into several cell types and are known to support regenerative processes by the release of immunomodulatory and trophic factors. In the liver, the space of Disse constitutes a stem cell niche that harbors stellate cells as liver resident MSCs. This perivascular niche is created by extracellular matrix proteins, sinusoidal endothelial cells, liver parenchymal cells and sympathetic nerve endings and establishes a microenvironment that is suitable to maintain stellate cells and to control their fate. The stem cell niche integrity is important for the behavior of stellate cells in the normal, regenerative, aged and diseased liver. The niche character of the space of Disse may further explain why the liver can become an organ of extra-medullar hematopoiesis and why this organ is frequently prone to tumor metastasis.

scholarly journals The Haematopoietic Stem Cell Niche: New Insights into the Mechanisms Regulating Haematopoietic Stem Cell Behaviour

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Andrew J. Lilly ◽  
William E. Johnson ◽  
Christopher M. Bunce
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Cell Types ◽  
Haematopoietic Stem Cell ◽  
Cell Behaviour ◽  
Ongoing Research ◽  
Hsc Niche ◽  
Numerous Cell ◽  
Cell Niche

The concept of the haematopoietic stem cell (HSC) niche was formulated by Schofield in the 1970s, as a region within the bone marrow containing functional cell types that can maintain HSC potency throughout life. Since then, ongoing research has identified numerous cell types and a plethora of signals that not only maintain HSCs, but also dictate their behaviour with respect to homeostatic requirements and exogenous stresses. It has been proposed that there are endosteal and vascular niches within the bone marrow, which are thought to regulate different HSC populations. However, recent data depicts a more complicated picture, with functional crosstalk between cells in these two regions. In this review, recent research into the endosteal/vascular cell types and signals regulating HSC behaviour are considered, together with the possibility of a single subcompartmentalised niche.

Breast cancer, stem cells, and the stem cell niche

2005 ◽  
Vol 8 (11) ◽  
Author(s):  
G. Chepko
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Mammary Tumorigenesis ◽  
Mammary Epithelium ◽  
Cell Types ◽  
Mammalian Development ◽  
Cell Proliferation And Differentiation ◽  
Neuronal Stem Cell ◽  
Stem And Progenitor Cells ◽  
Cell Niche

At least four cell types in mouse mammary epithelium, three in human, and three in cow are now known to be proliferation competent. Some evidence indicates that pregnancy may confer proliferative competency on a new cell type. These cells are widely seen as stem and progenitor cells that maintain the epithelium and produce lactational units during pregnancy. Evolutionarily conserved developmental signaling pathways active in germinal and neuronal stem cell proliferation and differentiation in drosophila and mammalian development are implicated in mammary tumorigenesis. In adult tissues this signaling is retained, is regulated by stem cell niches and operates to create new tissue and maintain tissue form and integrity. Disruption of this signaling may abrogate maintenance of the stem cell niche and lead to preneoplastic conditions.

scholarly journals Skeletal Muscle Stem Cell Niche from Birth to Old Age

2020 ◽  
Author(s):  
Madalina-Gabriela Barbu ◽  
Andreea-Elena Boboc ◽  
Lidia Filip ◽  
Oana-Larisa Bugnar ◽  
Dragos Cretoiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cells ◽  
Stem Cell Niche ◽  
Myogenic Differentiation ◽  
Cell Types ◽  
Undifferentiated Cells ◽  
Cell Niche ◽  
Therapeutic Tools

Stem cells are defined as undifferentiated cells that are able to unlimitedly renew themselves within controlled conditions and to differentiate into a multitude of mature cell types. Skeletal muscle stem cells, represented predominantly by satellite cells, show a variable capability of self-renewal and myogenic differentiation. They were found to be involved not only in the growth of myofibers during neonatal and juvenile life but also in the regeneration of skeletal muscles after an injury. The microenvironment in which stem cells are nourished and maintained dormant preceding division and differentiation is known as “niche.” The niche consists of myofibers, which are believed to modulate the active/inactive state of the stem cells, extracellular matrix, neural networks, blood vessels, and a multitude of soluble molecules. It was observed that changes in the composition of the niche have an impact on the stem cell functions and hierarchy. Furthermore, it seems that its layout is variable throughout the entire life, translating into a decrease in the regenerative capacity of satellite cells in aged tissues. The scope of this chapter is to provide a detailed view of the changes that occur in the skeletal stem cell niche during life and to analyze their implications on tissue regeneration. Future studies should focus on developing new therapeutic tools for diseases involving muscle atrophy.

scholarly journals Is Myelodysplasia a Consequence of Normal Aging?

2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Sonja Heibl ◽  
Reinhard Stauder ◽  
Michael Pfeilstöcker
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Risk Groups ◽  
Premature Aging ◽  
Cell Niche ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Abstract Purpose of Review To review available data on the relationship of MDS and aging and to address the question if biological changes of (premature) aging are a prerequisite for the development of MDS. Recent Findings Whereas the association of MDS with advanced age and some common biologic features of aging and MDS are well established, additional evidence for both, especially on the role of stem cells, the stem cell niche, and inflammation, has been recently described. Summary Biologically, many but not all drivers of aging also play a role in the development and propagation of MDS and vice versa. As a consequence, aging contributes to the development of MDS which can be seen as an interplay of clonal disease and normal and premature aging. The impact of aging may be different in specific MDS subtypes and risk groups.

scholarly journals Unsupervised cell interaction profiling reveals major architectural differences between small intestinal and colonic epithelial crypts

2020 ◽  
Author(s):  
Jason T. Serviss ◽  
Nathanael Andrews ◽  
Agneta B. Andersson ◽  
Ewa Dzwonkowska ◽  
Rosan Heijboer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Paneth Cell ◽  
Cell Types ◽  
Cell Interaction ◽  
Colonic Epithelium ◽  
Cellular Interactions ◽  
Small Intestinal ◽  
Cell Niche

AbstractCellular identity in complex multicellular organisms is strictly maintained over the course of life. This control is achieved in part by the organ structure itself, such that neighboring cells influence each other’s identity. However, large-scale investigation of the cellular interactome has been technically challenging. Here, we develop CIM-seq, an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between every cell type in a given tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution of these into their constituent cell types using machine learning. We use CIM-seq to define the cell interaction landscape of the mouse small intestinal and colonic epithelium, uncovering both known and novel interactions. Specifically, we find that the general architecture of the stem cell niche is radically different between the two tissues. In small intestine, the stem-Paneth cell interaction forms an exceptionally strong and exclusive niche, in which Paneth cells provide Wnt ligands1. In colonic epithelium, no similar compartment exists to support stem cells, and Wnt signaling is provided by a mesenchymal cell layer2,3. However, colonic stem cells are supported by an adjacent, previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is also highly upregulated during regeneration of colon epithelium. These results identify novel cellular interactions specific for the colonic stem cell niche and suggest an additional level of structural control in the colon. CIM-seq is broadly applicable to studies that aim to simultaneously investigate the constituent cell types and the global interaction profile in a specific tissue.

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