scholarly journals Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis

2022 ◽  
Vol 9 ◽  
Author(s):  
Fangyuan Shen ◽  
Yu Shi
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Bone Development ◽  
Lineage Tracing ◽  
Research Progress ◽  
Bone Homeostasis ◽  
Differentiation Potential ◽  
Cell Technology

Osteoblasts continuously replenished by osteoblast progenitor cells form the basis of bone development, maintenance, and regeneration. Mesenchymal stem cells (MSCs) from various tissues can differentiate into the progenitor cell of osteogenic lineage and serve as the main source of osteoblasts. They also respond flexibly to regenerative and anabolic signals emitted by the surrounding microenvironment, thereby maintaining bone homeostasis and participating in bone remodeling. However, MSCs exhibit heterogeneity at multiple levels including different tissue sources and subpopulations which exhibit diversified gene expression and differentiation capacity, and surface markers used to predict cell differentiation potential remain to be further elucidated. The rapid advancement of lineage tracing methods and single-cell technology has made substantial progress in the characterization of osteogenic stem/progenitor cell populations in MSCs. Here, we reviewed the research progress of scRNA-seq technology in the identification of osteogenic markers and differentiation pathways, MSC-related new insights drawn from single-cell technology combined with experimental technology, and recent findings regarding the interaction between stem cell fate and niche in homeostasis and pathological process.

Single-Cell Analysis of Lymphoid-Primed Multipotent Progenitors (LMPPs) Reveal Alterations in Lineage Commitment during Aging

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 244-244
Author(s):  
Sneha Borikar ◽  
Vivek Philip ◽  
Jennifer J. Trowbridge
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Conflicts Of Interest ◽  
Single Cells ◽  
Differentiation Potential ◽  
Increased Risk

Abstract During aging, the hematopoietic compartment undergoes lineage skewing, biased toward myeloid differentiation at the expense of lymphoid differentiation. This skewing clinically presents as impaired adaptive immunity and an increased risk of myeloproliferative disorders. However, little is known of the regulatory mechanisms underlying these changes in differentiation potential due in part to the inadequacy of current analytic techniques to evaluate lineage potency of individual progenitor cells. Recent demonstration that long-lived hematopoietic progenitor cells drive steady-state hematopoiesis has shifted focus onto the progenitor cell compartment to understand clonal dynamics of native hematopoiesis. Here, we critically assess the functional and molecular alterations in the multipotent progenitor cell pool with aging at the single-cell level. We developed novel in vitro and in vivo assays to define the heterogeneity of the LMPP population and test cell-fate potential from single cells. Our results demonstrate, for the first time, distinct, intrinsic lineage potential of single in vitro LMPPs at the cellular and molecular level. We find that clonal alterations in the lymphoid-primed multipotent progenitor (LMPP) compartment contributes to the functional alterations in hematopoiesis observed during aging. Unbiased single-cell transcriptome analysis reveals that true multipotential clones and lymphoid-restricted clones are reduced with aging, while bipotential and myeloid-restricted clones are modestly expanded. Furthermore, myeloid-restricted clones gain myc driver signatures, molecularly identifying clones emerging during aging that are susceptible to transformation. Our study reveals that aging alters the clonal composition of multipotential progenitor cells, directly contributing to the global loss of the lymphoid compartment and increased susceptibility to myeloid transformation. Disclosures No relevant conflicts of interest to declare.

TAMI-36. TAMEP ARE BRAIN TUMOR PARENCHYMAL CELLS CONTROLLING NEOPLASTIC ANGIOGENESIS AND PROGRESSION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi205-vi206
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Ines Hellmann ◽  
Rainer Glass
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Single Cell ◽  
Disease Progression ◽  
Progenitor Cell ◽  
Local Environment ◽  
Lineage Tracing ◽  
Immunofluorescence Analysis ◽  
Progenitor Cell Population ◽  
Parenchymal Cells

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor-parenchymal cells may promote specific phases of disease-progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Strikingly, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell-population, by conditional Sox2-knockout, drastically reduced glioblastoma-vascularization and -size. TAMEP manipulation profoundly altered vessel function and strongly attenuated the blood-tumor barrier. Hence, our data indicate TAMEP and their progenitors as new targets for glioblastoma therapy.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals Generative modeling of single-cell population time series for inferring cell differentiation landscapes

2020 ◽  
Author(s):  
Grace H.T. Yeo ◽  
Sachit D. Saksena ◽  
David K. Gifford
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Lineage Tracing ◽  
Model Framework ◽  
Modeling Framework ◽  
Generative Modeling ◽  
Model Complex

SummaryExisting computational methods that use single-cell RNA-sequencing for cell fate prediction either summarize observations of cell states and their couplings without modeling the underlying differentiation process, or are limited in their capacity to model complex differentiation landscapes. Thus, contemporary methods cannot predict how cells evolve stochastically and in physical time from an arbitrary starting expression state, nor can they model the cell fate consequences of gene expression perturbations. We introduce PRESCIENT (Potential eneRgy undErlying Single Cell gradIENTs), a generative modeling framework that learns an underlying differentiation landscape from single-cell time-series gene expression data. Our generative model framework provides insight into the process of differentiation and can simulate differentiation trajectories for arbitrary gene expression progenitor states. We validate our method on a recently published experimental lineage tracing dataset that provides observed trajectories. We show that this model is able to predict the fate biases of progenitor cells in neutrophil/macrophage lineages when accounting for cell proliferation, improving upon the best-performing existing method. We also show how a model can predict trajectories for cells not found in the model’s training set, including cells in which genes or sets of genes have been perturbed. PRESCIENT is able to accommodate complex perturbations of multiple genes, at different time points and from different starting cell populations. PRESCIENT models are able to recover the expected effects of known modulators of cell fate in hematopoiesis and pancreatic β cell differentiation.

scholarly journals Stem cell dynamics in mouse hair follicles: A story from cell division counting and single cell lineage tracing

Cell Cycle ◽  
2010 ◽  
Vol 9 (8) ◽  
pp. 1504-1510 ◽  
Author(s):  
Ying V. Zhang ◽  
Brian S. White ◽  
David I. Shalloway ◽  
Tudorita Tumbar
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Single Cell ◽  
Cell Lineage ◽  
Hair Follicles ◽  
Lineage Tracing ◽  
Cell Dynamics

scholarly journals Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis

Circulation ◽  
2020 ◽  
Vol 142 (21) ◽  
pp. 2045-2059 ◽  
Author(s):  
Gabriel F. Alencar ◽  
Katherine M. Owsiany ◽  
Santosh Karnewar ◽  
Katyayani Sukhavasi ◽  
Giuseppe Mocci ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Late Stage ◽  
Lineage Tracing ◽  
Stem Cell Marker ◽  
Cell Phenotype ◽  
Phenotypic Changes ◽  
Atherosclerotic Lesions ◽  
Single Cell Rna Sequencing

Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability. Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis. Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11 - , Lgals3 + population with a chondrocyte-like gene signature that was markedly reduced with SMC- Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene–positive, extracellular matrix-remodeling, “pioneer” cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization. Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3 + osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis.

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

2019 ◽  
Vol 46 (10) ◽  
pp. 489-498 ◽  
Author(s):  
Xiaona Zheng ◽  
Guangyu Zhang ◽  
Yandong Gong ◽  
Xiaowei Ning ◽  
Zhijie Bai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Hematopoietic Stem Cell ◽  
Lineage Tracing ◽  
Hematopoietic Stem ◽  
Stem Cell Fate

scholarly journals Identification of a basal stem cell subpopulation in the prostate via functional, lineage tracing and single-cell RNA-seq analyses

2019 ◽  
Author(s):  
Xue Wang ◽  
Haibo Xu ◽  
Chaping Cheng ◽  
Zhongzhong Ji ◽  
Huifang Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Basal Cell ◽  
Lineage Tracing ◽  
Cell Subpopulation ◽  
Basal Cells ◽  
Mesenchymal Transition ◽  
Genetic Ablation

AbstractThe basal cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation based on both immunocytochemical and cell lineage tracing analysis. The Zeb1+prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial cell types at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+basal cell subset shares gene expression signatures with both epithelial and mesenchymal cells and stands out uniquely among all the basal cell clusters. Moreover, Zeb1+epithelial cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.

scholarly journals OTME-1. TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii13-ii13
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Louisa von Baumgarten ◽  
Christian Schulz ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Single Cell ◽  
Progenitor Cell ◽  
Local Environment ◽  
Lineage Tracing ◽  
Strong Impact ◽  
Immunofluorescence Analysis ◽  
Progenitor Cell Population ◽  
Parenchymal Cells

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.

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