Cell contact induces multiple types of electrical excitability from ascidian two-cell embryos that are cleavage arrested and contain all cell fate determinants

2007 ◽  
Vol 293 (5) ◽  
pp. R1976-R1996
Author(s):  
Motoko Tanaka-Kunishima ◽  
Kunitaro Takahashi ◽  
Fumiyuki Watanabe
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Single Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Pair ◽  
Fate Determinants ◽  
Cell Fate Determinants

Ascidian early embryonic cells undergo cell differentiation without cell cleavage, thus enabling mixture of cell fate determinants in single cells, which will not be possible in mammalian systems. Either cell in a two-cell embryo (2C cell) has multiple fates and develops into any cell types in a tadpole. To find the condition for controlled induction of a specific cell type, cleavage-arrested cell triplets were prepared in various combinations. They were 2C cells in contact with a pair of anterior neuroectoderm cells from eight-cell embryos (2C-aa triplet), with a pair of presumptive notochordal neural cells (2C-AA triplet), with a pair of presumptive posterior epidermal cells (2C-bb triplet), and with a pair of presumptive muscle cells (2C-BB triplet). The fate of the 2C cell was electrophysiologically identified. When two-cell embryos had been fertilized 3 h later than eight-cell embryos and triplets were formed, the 2C cells became either anterior-neuronal, posterior-neuronal or muscle cells, depending on the cell type of the contacting cell pair. When two-cell embryos had been fertilized earlier than eight-cell embryos, most 2C cells became epidermal. When two- and eight-cell embryos had been simultaneously fertilized, the 2C cells became any one of three cell types described above or the epidermal cell type. Differentiation of the ascidian 2C cell into major cell types was reproducibly induced by selecting the type of contacting cell pair and the developmental time difference between the contacting cell pair and 2C cell. We discuss similarities between cleavage-arrested 2C cells and vertebrate embryonic stem cells and propose the ascidian 2C cell as a simple model for toti-potent stem cells.

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

scholarly journals The Stability of the Induced Epigenetic Programs

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Maria J. Barrero
Keyword(s):  
Stem Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Pluripotent Cells ◽  
Potential Applications ◽  
The Stability

For many years scientists have been attracted to the possibility of changing cell identity. In the last decades seminal discoveries have shown that it is possible to reprogram somatic cells into pluripotent cells and even to transdifferentiate one cell type into another. In view of the potential applications that generating specific cell types in the laboratory can offer for cell-based therapies, the next important questions relate to the quality of the induced cell types. Importantly, epigenetic aberrations in reprogrammed cells have been correlated with defects in differentiation. Therefore, a look at the epigenome and understanding how different regulators can shape it appear fundamental to anticipate potential therapeutic pitfalls. This paper covers these epigenetic aspects in stem cells, differentiation, and reprogramming and discusses their importance for the safety of in vitro engineered cell types.

scholarly journals Dynamic centriolar relocalization of Polo kinase and Centrobin in early mitosis primes centrosome asymmetry in fly neural stem cells

2018 ◽  
Author(s):  
Emmanuel Gallaud ◽  
Anjana Ramdas Nair ◽  
Nicole Horsley ◽  
Arnaud Monnard ◽  
Priyanka Singh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Structured Illumination ◽  
Structured Illumination Microscopy ◽  
Mitotic Kinase ◽  
Fate Determinants ◽  
Cell Fate Determinants ◽  
Daughter Centriole ◽  
Early Mitosis

Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain an older ‘mother’ and a younger ‘daughter’ centriole. Stem cells either inherit the mother or daughter centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the dynamics and mechanisms regulating centrosome asymmetry and biased centrosome segregation are unclear. Using 3D-Structured Illumination Microscopy (3D-SIM) and live cell imaging we show that in fly neural stem cells (neuroblasts) the mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) dynamically relocalize from the mother to the daughter centriole during mitosis. This mechanism generates a centrosome, containing two molecularly distinct centrioles by telophase. Cnb’s timely relocalization is regulated by Polo-mediated phosphorylation whereas Polo’s daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic protein mislocalization experiments we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle orientation.

scholarly journals ProtAnno, an Automated Cell Type Annotation Tool for Single Cell Proteomics Data that Integrates Information from Multiple Reference Sources

2021 ◽  
Author(s):  
Wenxuan Deng ◽  
Biqing Zhu ◽  
Seyoung Park ◽  
Tomokazu S. Sumida ◽  
Avraham Unterman ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cells ◽  
Earth Metal ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Proteomics Data ◽  
Data Annotation ◽  
Different Cell Types ◽  
Unique Molecular Identifier

Compared with sequencing-based global genomic profiling, cytometry labels targeted surface markers on millions of cells in parallel either by conjugated rare earth metal particles or Unique Molecular Identifier (UMI) barcodes. Correct annotation of these cells to specific cell types is a key step in the analysis of these data. However, there is no computational tool that automatically annotates single cell proteomics data for cell type inference. In this manuscript, we propose an automated single cell proteomics data annotation approach called ProtAnno to facilitate cell type assignments without laborious manual gating. ProtAnno is designed to incorporate information from annotated single cell RNA-seq (scRNA-seq), CITE-seq, and prior data knowledge (which can be imprecise) on biomarkers for different cell types. We have performed extensive simulations to demonstrate the accuracy and robustness of ProtAnno. For several single cell proteomics datasets that have been manually labeled, ProtAnno was able to correctly label most single cells. In summary, ProtAnno offers an accurate and robust tool to automate cell type annotations for large single cell proteomics datasets, and the analysis of such annotated cell types can offer valuable biological insights.

Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells

2018 ◽  
Vol 144 (10) ◽  
pp. 1933-1944 ◽  
Author(s):  
Banaja P. Dash ◽  
Tina M. Schnöder ◽  
Carolin Kathner ◽  
Juliane Mohr ◽  
Sönke Weinert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cell Fate ◽  
Hematopoietic Stem ◽  
And Migration ◽  
Fate Determinants ◽  
Cell Fate Determinants

scholarly journals Neural Stem Cells inDrosophila: Molecular Genetic Mechanisms Underlying Normal Neural Proliferation and Abnormal Brain Tumor Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Nidhi Saini ◽  
Heinrich Reichert
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Tumor Formation ◽  
Asymmetric Cell Divisions ◽  
Fate Determinants ◽  
Cell Fate Determinants

Neural stem cells inDrosophilaare currently one of the best model systems for understanding stem cell biology during normal development and during abnormal development of stem cell-derived brain tumors. InDrosophilabrain development, the proliferative activity of neural stem cells called neuroblasts gives rise to both the optic lobe and the central brain ganglia, and asymmetric cell divisions are key features of this proliferation. The molecular mechanisms that underlie the asymmetric cell divisions by which these neuroblasts self-renew and generate lineages of differentiating progeny have been studied extensively and involve two major protein complexes, the apical complex which maintains polarity and controls spindle orientation and the basal complex which is comprised of cell fate determinants and their adaptors that are segregated into the differentiating daughter cells during mitosis. Recent molecular genetic work has establishedDrosophilaneuroblasts as a model for neural stem cell-derived tumors in which perturbation of key molecular mechanisms that control neuroblast proliferation and the asymmetric segregation of cell fate determinants lead to brain tumor formation. Identification of novel candidate genes that control neuroblast self-renewal and differentiation as well as functional analysis of these genes in normal and tumorigenic conditions in a tissue-specific manner is now possible through genome-wide transgenic RNAi screens. These cellular and molecular findings inDrosophilaare likely to provide valuable genetic links for analyzing mammalian neural stem cells and tumor biology.

An RNA Interference Screen Identifies the Cell Fate Determinants Msi2 and Prox1 as Novel Regulators of Hematopoietic Stem Cell Self-Renewal.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 394-394
Author(s):  
Kristin J Hope ◽  
Sonia Cellot ◽  
Stephen Ting ◽  
Guy Sauvageau
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Control Shrna ◽  
Fate Determinants ◽  
Cell Fate Determinants

Abstract Abstract 394 Hematopoietic stem cells (HSC) can not yet be unambiguously prospectively identified, a fact which has made it difficult to determine whether a segregation of cell fate determinants underlies the asymmetric/symmetric self-renewal of these cells or whether deregulation of such determinants could contribute to the pathogenesis of hematopoietic malignancies by inducing constitutive symmetric self-renewal divisions. We have addressed these questions through a functional genetics approach taking advantage of systematic RNAi to evaluate the function of conserved polarity factors and cell fate determinants in HSCs. From a list of 72 of such factors identified in the literature, 30 murine homologues were chosen based on their differentially higher level of expression in HSC-enriched populations as measured by qRT-PCR. For each candidate we designed 3 unique short hairpin RNA (shRNA) encoding retroviral constructs also carrying EGFP for the purposes of following transduced cells. Primitive hematopoietic cells enriched for HSC were infected at high efficiency with the library in an arrayed 96-well format and their in vivo reconstituting potential was then evaluated through competitive repopulating unit assays. Genes for which shRNA vectors altered late transplant EGFP levels below or above thresholds as defined by a control shRNA to luciferase were considered as hits. Using this approach, we identified and comprehensively validated 4 genes, including the RNA binding protein Msi2, for which shRNA-mediated depletion dramatically impairs repopulation but does not induce cell death or a cell cycle block. Importantly, we show that the loss in the repopulating ability of these shRNA transduced cells is mediated at the stem cell level and is not due to progenitor or downstream cell toxicity or to any defect in the process of bone marrow homing. Subsequent expression profiling indicated that Msi2 is also upregulated in HOXB4-overexpressing symmetrically expanding HSC in line with our findings that it functions as a positive HSC regulator and further suggesting that it represents a potential novel HSC marker. As well as finding HSC agonists, the RNAi screen identified the homeodomain containing transcription factor Prox1 as a negative HSC regulator since its shRNA-mediated transcript loss consistently led to the dramatic in vivo accumulation of EGFP+ transduced cells. Grafts comprised of Prox1 shRNA-transduced cells did not exhibit any lineage skewing however, repeatedly contained an average of 10-fold more primitive Lin-Sca+CD150+48- cells as compared to non-transduced donor cells within the same recipient or to control shRNA-luciferase grafts indicating Prox1 knockdown leads to a significant in vivo expansion of phenotypic HSCs. Moreover, following a 7 day in vitro culture, cells infected with shRNAs to Prox1 were both morphologically and immunophenotypically more primitive than control cells and when transplanted at this time yielded a significantly enhanced engraftment level relative to control shRNAs (51+/-6% GFP vs 8+/-3% GFP). These results further suggest that Prox1 reduction by RNAi expands functional HSCs in vitro. Together these findings have identified conserved cell fate determinants as important and novel regulators of murine hematopoietic stem cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jose Alquicira-Hernandez ◽  
Anuja Sathe ◽  
Hanlee P. Ji ◽  
Quan Nguyen ◽  
Joseph E. Powell
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Single Cells ◽  
Prediction Method ◽  
Cell Types ◽  
Pancreatic Tissue ◽  
Specific Cell ◽  
Cell Type ◽  
Learning Probability ◽  
Dimension Space

AbstractSingle-cell RNA sequencing has enabled the characterization of highly specific cell types in many tissues, as well as both primary and stem cell-derived cell lines. An important facet of these studies is the ability to identify the transcriptional signatures that define a cell type or state. In theory, this information can be used to classify an individual cell based on its transcriptional profile. Here, we present scPred, a new generalizable method that is able to provide highly accurate classification of single cells, using a combination of unbiased feature selection from a reduced-dimension space, and machine-learning probability-based prediction method. We apply scPred to scRNA-seq data from pancreatic tissue, mononuclear cells, colorectal tumor biopsies, and circulating dendritic cells and show that scPred is able to classify individual cells with high accuracy. The generalized method is available at https://github.com/powellgenomicslab/scPred/.

scholarly journals Hematopoiesis: A Layered Organization Across Chordate Species

2020 ◽  
Vol 8 ◽  
Author(s):  
Ramy Elsaid ◽  
Francisca Soares-da-Silva ◽  
Marcia Peixoto ◽  
Dali Amiri ◽  
Nathan Mackowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Immune Cells ◽  
Single Cells ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Lymphoid Cells ◽  
Specific Cell ◽  
Hematopoietic Stem ◽  
Hematopoietic System

The identification of distinct waves of progenitors during development, each corresponding to a specific time, space, and function, provided the basis for the concept of a “layered” organization in development. The concept of a layered hematopoiesis was established by classical embryology studies in birds and amphibians. Recent progress in generating reliable lineage tracing models together with transcriptional and proteomic analyses in single cells revealed that, also in mammals, the hematopoietic system evolves in successive waves of progenitors with distinct properties and fate. During embryogenesis, sequential waves of hematopoietic progenitors emerge at different anatomic sites, generating specific cell types with distinct functions and tissue homing capacities. The first progenitors originate in the yolk sac before the emergence of hematopoietic stem cells, some giving rise to progenies that persist throughout life. Hematopoietic stem cell-derived cells that protect organisms against environmental pathogens follow the same sequential strategy, with subsets of lymphoid cells being only produced during embryonic development. Growing evidence indicates that fetal immune cells contribute to the proper development of the organs they seed and later ensure life-long tissue homeostasis and immune protection. They include macrophages, mast cells, some γδ T cells, B-1 B cells, and innate lymphoid cells, which have “non-redundant” functions, and early perturbations in their development or function affect immunity in the adult. These observations challenged the view that all hematopoietic cells found in the adult result from constant and monotonous production from bone marrow-resident hematopoietic stem cells. In this review, we evaluate evidence for a layered hematopoietic system across species. We discuss mechanisms and selective pressures leading to the temporal generation of different cell types. We elaborate on the consequences of disturbing fetal immune cells on tissue homeostasis and immune development later in life.

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