Pluripotency and the origin of animal multicellularity

The most widely held, but rarely tested, hypothesis for the origin of animals is that they evolved from a unicellular ancestor with an apical cilium surrounded by a microvillar collar that structurally resembled present-day sponge choanocytes and choanoflagellates1–4. Here we test this traditional view of the origin of the animal kingdom by comparing the transcriptomes, fates and behaviours of the three primary sponge cell types – choanocytes, pluripotent mesenchymal archeocytes and epithelial pinacocytes – with choanoflagellates and other unicellular holozoans. Unexpectedly, we find the transcriptome of sponge choanocytes is the least similar to the transcriptomes of choanoflagellates and is significantly enriched in genes unique to either animals or to sponges alone. In contrast, pluripotent archeocytes upregulate genes controlling cell proliferation and gene expression, as in other metazoan stem cells and in the proliferating stages of two closely-related unicellular holozoans, including a colonial choanoflagellate. In the context of the body plan of the sponge, Amphimedon queenslandica, we show that choanocytes appear late in development and are the result of a transdifferentiation event. They exist in a metastable state and readily transdifferentiate into archeocytes, which can differentiate into a range of other cell types. These sponge cell type conversions are similar to the temporal cell state changes that occur in many unicellular holozoans5. Together, these analyses offer no support for the homology of sponge choanocytes and choanoflagellates, nor for the view that the first multicellular animals were simple balls of cells with limited capacity to differentiate. Instead, our results are consistent with the first animal cell being able to transition between multiple states in a manner similar to modern transdifferentiating and stem cells.

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Abstract 17093: Human Neonatal Cardiac Mesenchymal Stem Cells Demonstrates Superior Cardiac Regenerative Abilities Compared to Other Stem Cells

Circulation ◽

10.1161/circ.142.suppl_3.17093 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Muthukumar Gunasekaran ◽

Rachana Mishra ◽

Progyaparamita Saha ◽

Xuebin Fu ◽

Mohamed Abdullah ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Inflammatory Cytokines ◽

Cell Types ◽

Wild Type ◽

Cell Type ◽

Anti Inflammatory ◽

Stem Cell Type

Stem cells transplantation is being explored as an effective therapy for heart diseases. However, majority of stem cell therapies for adult patients with myocardial infarction (MI) had mixed and inconsistent results implying chronological age may influence the effectiveness of regenerative therapies. Therefore, herein, we performed a head-to-head comparison between different, well-studied stem cell types to identify the superior regenerative cell type using rodent MI model.After our standard characterization for each stem cell type (FACS for cell surface markers), 1 million neonatal Cardiac Mesenchymal Stem cells (nMSCs), adult MSCs (aMSCs), adult derived cardiosphere derived cells (aCDCs), umbilical cord derived cells (UCBCs), Bone Marrow derived Mesenchymal Stem cells (BM-MSCs), or cell-free Iscove Modified Dulbecco Medium (IMDM as placebo control) were injected into athymic rat myocardial infarct model. Although all the tested groups significantly improved ejection fraction, nMSCs outperformed other stem cells in cardiac functional recovery. Additionally, nMSCs also showed significant increased cardiac functional recovery compared to aMSCs in wild type rat MI model. Mason trichrome staining with heart sections revealed that decreased fibrosis was evident on nMSCs injection compared to aMSCs in both athymic and wild type rat MI model. Myocardial sections from rats received nMSCs showed significantly reduced M1 macrophages (inflammatory) and increased M2 macrophages (anti-inflammatory) compared with sections from rats having received aMSCs and IMDM control. Pro and anti-inflammatory cytokines analyzed on sera collected on day 2 and 7 revealed that anti-inflammatory cytokine (IL10) was significantly increased and inflammatory cytokines (IL4 and IL12) reduced in nMSCs compared to aMSCs transplanted MI rat model.In conclusion, nMSCs demonstrated superior functional abilities, reduced fibrosis, inflammatory cells and cytokines compared to all the other cell types and with aMSCs demonstrating that nMSCs is an ideal stem cell type for therapeutic application in myocardial infarction.

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Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner

Journal of Virology ◽

10.1128/jvi.01946-20 ◽

2021 ◽

Author(s):

Guoxun Wang ◽

Christina Zarek ◽

Tyron Chang ◽

Lili Tao ◽

Alexandria Lowe ◽

...

Keyword(s):

B Cells ◽

Cell Types ◽

The Body ◽

Receptor Expression ◽

Conditional Knockout ◽

Interleukin 4 ◽

Virus Reactivation ◽

Cell Type ◽

Murine Gammaherpesvirus ◽

Cell Type Specific

Gammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi’s sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation, but that it was dispensable on B cells. We further demonstrated that the transcription factor, STAT6, which is downstream of the IL-4 receptor and binds virus gene 50 N4/N5 promoter in macrophages, did not bind to the virus gene 50 N4/N5 promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may only affect latent virus in particular cell types, but not in others. Importance Herpesviruses establish life-long quiescent infections in specific cells in the body, and only reactivate to produce infectious virus when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus. However, herpesviruses establish latency in multiple cell types in their hosts. Using murine gammaherpesvirus-68 (MHV68) and conditional knockout mice, we examined the cell type specificity of a particular reactivation signal, interleukin-4 (IL-4). We found that IL-4 only induced herpesvirus reactivation from macrophages, but not from B cells. This work indicates that regulation of virus latency and reactivation is cell type specific. This has important implications for therapies aimed at either promoting or inhibiting reactivation for the control or elimination of chronic viral infections.

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Modulating cell state to enhance suspension expansion of human pluripotent stem cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1714099115 ◽

2018 ◽

Vol 115 (25) ◽

pp. 6369-6374 ◽

Cited By ~ 12

Author(s):

Yonatan Y. Lipsitz ◽

Curtis Woodford ◽

Ting Yin ◽

Jacob H. Hanna ◽

Peter W. Zandstra

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Large Scale ◽

Cell Types ◽

Human Pluripotent Stem Cells ◽

The Body ◽

Altered Expression ◽

Pancreatic Progenitors ◽

Erk Inhibition

The development of cell-based therapies to replace missing or damaged tissues within the body or generate cells with a unique biological activity requires a reliable and accessible source of cells. Human pluripotent stem cells (hPSC) have emerged as a strong candidate cell source capable of extended propagation in vitro and differentiation to clinically relevant cell types. However, the application of hPSC in cell-based therapies requires overcoming yield limitations in large-scale hPSC manufacturing. We explored methods to convert hPSC to alternative states of pluripotency with advantageous bioprocessing properties, identifying a suspension-based small-molecule and cytokine combination that supports increased single-cell survival efficiency, faster growth rates, higher densities, and greater expansion than control hPSC cultures. ERK inhibition was found to be essential for conversion to this altered state, but once converted, ERK inhibition led to a loss of pluripotent phenotype in suspension. The resulting suspension medium formulation enabled hPSC suspension yields 5.7 ± 0.2-fold greater than conventional hPSC in 6 d, for at least five passages. Treated cells remained pluripotent, karyotypically normal, and capable of differentiating into all germ layers. Treated cells could also be integrated into directed differentiated strategies as demonstrated by the generation of pancreatic progenitors (NKX6.1+/PDX1+ cells). Enhanced suspension-yield hPSC displayed higher oxidative metabolism and altered expression of adhesion-related genes. The enhanced bioprocess properties of this alternative pluripotent state provide a strategy to overcome cell manufacturing limitations of hPSC.

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A community-based transcriptomics classification and nomenclature of neocortical cell types

Nature Neuroscience ◽

10.1038/s41593-020-0685-8 ◽

2020 ◽

Vol 23 (12) ◽

pp. 1456-1468 ◽

Cited By ~ 8

Author(s):

Rafael Yuste ◽

Michael Hawrylycz ◽

Nadia Aalling ◽

Argel Aguilar-Valles ◽

Detlev Arendt ◽

...

Keyword(s):

Data Aggregation ◽

Developmental Stages ◽

Cell Types ◽

The Body ◽

Cortical Circuits ◽

Cell Type ◽

Community Based ◽

Cortical Cells ◽

Molecular Features ◽

Definition Of

AbstractTo understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

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Chemical compound-based direct reprogramming for future clinical applications

Bioscience Reports ◽

10.1042/bsr20171650 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 10

Author(s):

Yukimasa Takeda ◽

Yoshinori Harada ◽

Toshikazu Yoshikawa ◽

Ping Dai

Keyword(s):

Stem Cells ◽

Transcription Factors ◽

Chemical Compound ◽

Chemical Compounds ◽

Cell Types ◽

Direct Reprogramming ◽

Cell Type ◽

Promising Alternative ◽

Cell Functions ◽

Transplantation Therapy

Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy.

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Effects of Aging and TGF-Beta 3 on Chondrocyte and Mesenchymal Stem Cell Matrix Formation

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19517 ◽

2010 ◽

Author(s):

Isaac E. Erickson ◽

Steven C. van Veen ◽

Swarnali Sengupta ◽

Sydney R. Kestle ◽

Jason A. Burdick ◽

...

Keyword(s):

Stem Cells ◽

Articular Chondrocytes ◽

Cell Types ◽

Matrix Proteins ◽

Cell Type ◽

Cell Matrix ◽

Age Related ◽

Cartilage Restoration ◽

Effects Of Aging

Articular cartilage pathology is common in the aged population. Numerous studies have shown that aged chondrocytes (CHs) are inferior to juvenile CHs in their ability to proliferate and produce cartilage-specific extracellular matrix proteins, potentially limiting their use in tissue engineering applications for cartilage restoration [1,2]. Mesenchymal stem cells (MSCs) are an alternative cell type that can be expanded in vitro while maintaining their ability to differentiate into cell types comparable to articular chondrocytes. However, organismal aging also influences human MSC proliferation [3,4] and multi-potential differentiation [5], though for chondrogenesis these findings are mixed, with some suggesting that aged progenitor cells retain their chondrogenic capacity [6]. The objective of this study was to assess age related differences in donor-matched CH and MSC potential for chondrogenic repair. In addition, the effects of the chondrogenic growth factor TGF-β3 on CHs and MSCs were evaluated.

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Functions of p53 in pluripotent stem cells

Protein & Cell ◽

10.1007/s13238-019-00665-x ◽

2019 ◽

Vol 11 (1) ◽

pp. 71-78 ◽

Cited By ~ 10

Author(s):

Xuemei Fu ◽

Shouhai Wu ◽

Bo Li ◽

Yang Xu ◽

Jingfeng Liu

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Mammalian Cells ◽

Genomic Stability ◽

Cell Types ◽

The Body ◽

Great Promise ◽

Primary Role ◽

Cycle Arrest ◽

Clinical Potential

Abstract Pluripotent stem cells (PSCs) are capable of unlimited self-renewal in culture and differentiation into all functional cell types in the body, and thus hold great promise for regenerative medicine. To achieve their clinical potential, it is critical for PSCs to maintain genomic stability during the extended proliferation. The critical tumor suppressor p53 is required to maintain genomic stability of mammalian cells. In response to DNA damage or oncogenic stress, p53 plays multiple roles in maintaining genomic stability of somatic cells by inducing cell cycle arrest, apoptosis, and senescence to prevent the passage of genetic mutations to the daughter cells. p53 is also required to maintain the genomic stability of PSCs. However, in response to the genotoxic stresses, a primary role of p53 in PSCs is to induce the differentiation of PSCs and inhibit pluripotency, providing mechanisms to maintain the genomic stability of the self-renewing PSCs. In addition, the roles of p53 in cellular metabolism might also contribute to genomic stability of PSCs by limiting oxidative stress. In summary, the elucidation of the roles of p53 in PSCs will be a prerequisite for developing safe PSC-based cell therapy.

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Light microscopical and cytochemical study on the adhesive and epidermal gland cell secretions of the branchiobdellid Cambarincola fallax (Annelida: Clitellata)

Canadian Journal of Zoology ◽

10.1139/z88-303 ◽

1988 ◽

Vol 66 (9) ◽

pp. 2057-2064 ◽

Cited By ~ 14

Author(s):

S. R. Gelder ◽

J. P. Rowe

Keyword(s):

Basic Protein ◽

Gland Cell ◽

Attachment Site ◽

Cell Types ◽

The Body ◽

Protein Component ◽

Cell Type ◽

Gland Cells ◽

Adhesive Organs ◽

Epidermal Gland

Eight types of gland cells are present in six different epidermal glands in the branchiobdellid Cambarincola fallax. The anterior and posterior adhesive organs are both composed of viscid and releaser adhesive gland cell types, and their secretions open onto the anterior attachment site on the ventral surface of the ventral peristomial lip and onto the posterior attachment disc, respectively. The secretion granules of the viscid gland cell type are composed of neutral mucosubstances with basic proteins containing arginine and (or) lysine; the releaser gland cell type contains basic proteinaceous granules with a tryptophan component. These adhesive glands are very similar to duo-gland adhesive organs described elsewhere. Use of the term "sucker" should be discontinued as there is no suctorial mechanism at the anterior attachment site and only circumstantial evidence of such action at the posterior disc. Two epidermal gland cell types occur together in groups of two to four cells at sites scattered over the body surface except in trunk segments 6 and 7. One of these epidermal gland cell types produces granular secretions formed of neutral mucosubstances with a basic protein component, and the other produces globular secretions composed of a carboxylated acid mucosubstance. Secretions from the peristomial gland cells open onto the dorsal and ventral lips. The posterolateral gland cells form three pairs: two pairs in segment 8 and one pair in segment 9. Both peristomial and posterolateral gland cells have granular secretions composed of neutral mucosubstances with a basic protein component. The two types of clitellar gland cells are arranged in groups of 7 to 13 cells with a granular secretion type predominating over one with globular secretions. The granular type consists of neutral mucosubstances with amyloid-like and strong basic protein components, and the globular type consists of a carboxylated acid mucosubstance with a nonbasic protein component.

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Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00416.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. G592-G605 ◽

Cited By ~ 13

Author(s):

Kunihiro Kishida ◽

Sarah C. Pearce ◽

Shiyan Yu ◽

Nan Gao ◽

Ronaldo P. Ferraris

Keyword(s):

Stem Cells ◽

Cell Types ◽

Paneth Cells ◽

Nutrient Sensing ◽

Intestinal Stem Cells ◽

Intestinal Cell ◽

Cell Type ◽

Extended Lifespan ◽

Small Intestinal ◽

Single Cell Type

Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers. We identified nutrient sensing cell type(s) by increased expression of fructolytic genes in response to a fructose challenge. Organoids comprised primarily of enterocytes, Paneth, or goblet, but not ISC, cells responded specifically to fructose without affecting nonfructolytic genes. Sensing was independent of Wnt and Notch modulators and of glucose concentrations in the medium but required fructose absorption and metabolism. More mature enterocyte- and goblet-enriched organoids exhibited stronger fructose responses. Remarkably, enterocyte organoids, upon forced dedifferentiation to reacquire ISC characteristics, exhibited a markedly extended lifespan and retained fructose sensing ability, mimicking responses of some dedifferentiated cancer cells. Using an innovative approach, we discovered that nutrient sensing is likely repressed in progenitor ISCs then irreversibly derepressed during specification into sensing-competent absorptive or secretory lineages, the surprising capacity of Paneth and goblet cells to detect fructose, and the important role of differentiation in modulating nutrient sensing. NEW & NOTEWORTHY Small intestinal stem cells differentiate into several cell types transiently populating the villi. We used specialized organoid cultures each comprised of a single cell type to demonstrate that 1) differentiation seems required for nutrient sensing, 2) secretory goblet and Paneth cells along with enterocytes sense fructose, suggesting that sensing is acquired after differentiation is triggered but before divergence between absorptive and secretory lineages, and 3) forcibly dedifferentiated enterocytes exhibit fructose sensing and lifespan extension.

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A REPORT ON STEM CELLS AND THEIR APPLICATIONS

10.36106/ijar/2010867 ◽

2020 ◽

pp. 1-2

Author(s):

Shantha A R

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Building Blocks ◽

Cell Types ◽

The Body ◽

Cell Therapies ◽

Undifferentiated Cells ◽

The Cost

Stem cells are the building blocks of life. They have remarkable potential to regenerate and develop into many different cell types in the body during early life and growth. They are also a class of undifferentiated cells that are able to be differentiated into specialized cells types. Stem cells are characterized by certain features such as totipotency, pluripotency, multipotency, oligopotent and unipotency. The history of stem cell research had an embryonic beginning in the mid 1800s with the discovery that few cells could generate other cells. In the 1900s the first stem cells were discovered when it was found that cells generate blood cells. Nowadays, stem cell therapy is under research and till now, a very few stem cell therapies have been regarded as safe and successful. It is also found that stem cell therapy cast a number of side effects too. The cost of the procedure too is expensive and is not easily affordable.

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