scholarly journals The people behind the papers – Awais Javed and Michel Cayouette

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev196469
Keyword(s):  
Clinical Research ◽  
Progenitor Cells ◽  
Cell Types ◽  
Research Unit ◽  
Chronological Order ◽  
The People ◽  
Distinct Cell ◽  
Mammalian Retina ◽  
Mcgill University

ABSTRACTThe mammalian retina contains a variety of functionally distinct cell types that are generated by progenitor cells in a specific chronological order. A new paper in Development probes the role of the POU-homeodomain factors Pou2f1 and Pou2f2 in the timely generation of cone photoreceptors in mice. We caught up with first author and PhD student Awais Javed and his supervisor Michel Cayouette (Director of the Cellular Neurobiology Research Unit at the Montreal Clinical Research Institute, Professor at the Université de Montréal and Adjunct Professor at McGill University) to hear more about their work.

scholarly journals Intravital 2-photon imaging reveals distinct morphology and infiltrative properties of glioblastoma-associated macrophages

2019 ◽  
Vol 116 (28) ◽  
pp. 14254-14259 ◽  
Author(s):  
Zhihong Chen ◽  
James L. Ross ◽  
Dolores Hambardzumyan
Keyword(s):  
Cell Types ◽  
Lineage Tracing ◽  
Response To Therapy ◽  
Vascular Endothelial ◽  
Distinct Cell ◽  
Attractive Option ◽  
Endothelial Growth Factor ◽  
Distinct Morphology ◽  
Cx3cr1 Expression

Characterized by a dismal survival rate and limited response to therapy, glioblastoma (GBM) remains one of the most aggressive human malignancies. Recent studies of the role of tumor-associated macrophages (TAMs) in the progression of GBMs have demonstrated that TAMs are significant contributors to tumor growth, invasion, and therapeutic resistance. TAMs, which include brain-resident microglia and circulating bone marrow derived-monocytes (BMDMs), are typically grouped together in histopathological and molecular analyses due to the lack of reliable markers of distinction. To develop more effective therapies aimed at specific TAM populations, we must first understand how these cells differ both morphologically and behaviorally. Furthermore, we must develop a deeper understanding of the mechanisms encouraging their infiltration and how these mechanisms can be therapeutically exploited. In this study, we combined immunocompetent lineage tracing mouse models of GBM with high-resolution open-skull 2-photon microscopy to investigate the phenotypical and functional characteristics of TAMs. We demonstrate that TAMs are composed of 2 morphologically distinct cell types that have differential migratory propensities. We show that BMDMs are smaller, minimally branched cells that are highly migratory compared with microglia, which are larger, highly branched stationary cells. In addition, 2 populations of monocytic macrophages were observed that differed in terms of CX3CR1 expression and migratory capacity. Finally, we demonstrate the efficacy of anti-vascular endothelial growth factor A blockade for prohibiting TAM infiltration, especially against BMDMs. Taken together, our data clearly define characteristics of individual TAM populations and suggest that combination therapy with antivascular and antichemotaxis therapy may be an attractive option for treating these tumors.

scholarly journals An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 409-429
Author(s):  
Matthew B. Lohse ◽  
Lucas R. Brenes ◽  
Naomi Ziv ◽  
Michael B. Winter ◽  
Charles S. Craik ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Specific Expression ◽  
Environmental Signals ◽  
Single Genome ◽  
Distinct Cell ◽  
Secreted Proteases ◽  
Expression Program

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease (SAP) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types.

scholarly journals Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev188730 ◽  
Author(s):  
Awais Javed ◽  
Pierre Mattar ◽  
Suying Lu ◽  
Kamil Kruczek ◽  
Magdalena Kloc ◽  
...  
Keyword(s):  
Cell Types ◽  
Mouse Retina ◽  
Cone Photoreceptor ◽  
Chronological Order ◽  
Temporal Window ◽  
General Role ◽  
Cone Production ◽  
Regulatory Cascade ◽  
The People ◽  
Temporal Identity

ABSTRACTMultipotent retinal progenitor cells (RPCs) generate various cell types in a precise chronological order, but how exactly cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU-homeodomain factors Pou2f1/Pou2f2, the homologs of Drosophila temporal identity factors nub/pdm2, regulate the timely production of cones in mice. Forcing sustained expression of Pou2f1 or Pou2f2 in RPCs expands the period of cone production, whereas misexpression in late-stage RPCs triggers ectopic cone production at the expense of late-born fates. Mechanistically, we report that Pou2f1 induces Pou2f2 expression, which binds to a POU motif in the promoter of the rod-inducing factor Nrl to repress its expression. Conversely, conditional inactivation of Pou2f2 in RPCs increases Nrl expression and reduces cone production. Finally, we provide evidence that Pou2f1 is part of a cross-regulatory cascade with the other temporal identity factors Ikzf1 and Casz1. These results uncover Pou2f1/2 as regulators of the temporal window for cone genesis and, given their widespread expression in the nervous system, raise the possibility of a general role in temporal patterning.This article has an associated ‘The people behind the papers’ interview.

scholarly journals The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

2021 ◽  
Vol 10 (15) ◽  
pp. 3348
Author(s):  
Angela Quispe-Salcedo ◽  
Hayato Ohshima
Keyword(s):  
Dendritic Cells ◽  
Cell Types ◽  
Tooth Injuries ◽  
Tertiary Dentin ◽  
Distinct Cell ◽  
Reparative Dentin ◽  
Pulp Cells ◽  
Antigen Presenting

The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of “dentin-pulp immunology” is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.

scholarly journals Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.

1991 ◽  
Vol 113 (4) ◽  
pp. 919-929 ◽  
Author(s):  
E A Wayner ◽  
R A Orlando ◽  
D A Cheresh
Keyword(s):  
Cell Surface ◽  
Lung Carcinoma ◽  
Cell Attachment ◽  
Cell Types ◽  
Carcinoma Cells ◽  
Lung Carcinoma Cells ◽  
Distinct Cell ◽  
Contact Distribution ◽  
Alpha V Beta 3

We investigated the role of the integrins alpha v beta 3 and alpha v beta 5 in mediating vitronectin adhesion of three phenotypically distinct cell types. M21 human melanoma cells and H2981 lung carcinoma cells use both alpha v-containing integrins in adhering to vitronectin while UCLA-P3 lung carcinoma cells adhere exclusively with alpha v beta 5. Specifically, monoclonal antibodies directed to functional epitopes on both receptors were required to block adhesion of M21 or H2981 cells while adhesion of UCLA-P3 cells to vitronectin could be blocked with a monoclonal antibody to alpha v beta 5. Although both receptors are involved in M21 and H2981 cell adhesion to vitronectin, only alpha v beta 3 can be detected in focal contacts, colocalizing with vinculin, talin, and the ends of actin filaments, while alpha v beta 5 shows a distinct, nonfocal contact, distribution on the cell surface. These results provide the first evidence that two homologous integrins that recognize the same ligand distribute differentially on the cell surface.

scholarly journals RUN and FYVE domain–containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4

2015 ◽  
Vol 210 (7) ◽  
pp. 1133-1152 ◽  
Author(s):  
Seigo Terawaki ◽  
Voahirana Camosseto ◽  
Francesca Prete ◽  
Till Wenger ◽  
Alexia Papadopoulos ◽  
...  
Keyword(s):  
Immune Cells ◽  
Pathogen Detection ◽  
Cell Types ◽  
Interleukin 4 ◽  
Autophagosome Formation ◽  
Autophagy Flux ◽  
Mhc Ii ◽  
Fyve Domain ◽  
Distinct Cell

Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.

Hedgehog signaling patterns the tracheal branches

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1599-1606 ◽  
Author(s):  
L. Glazer ◽  
B.Z. Shilo
Keyword(s):  
Cell Migration ◽  
Hedgehog Signaling ◽  
Egf Receptor ◽  
Cell Types ◽  
Fixed Number ◽  
Branching Pattern ◽  
Tracheal System ◽  
Tracheal Cell ◽  
Distinct Cell

The elaborate branching pattern of the Drosophila tracheal system originates from ten tracheal placodes on both sides of the embryo, each consisting of about 80 cells. Simultaneous cell migration from each tracheal pit in six different directions gives rise to the stereotyped branching pattern. Each branch contains a fixed number of cells. Previous work has shown that in the dorsoventral axis, localized activation of the Dpp, Wnt and EGF receptor (DER) pathways, subdivides the tracheal pit into distinct domains. We present the role of the Hedgehog (Hh) signaling system in patterning the tracheal branches. Hh is expressed in segmental stripes abutting the anterior border of the tracheal placodes. Induction of patched expression, which results from activation by Hh, demonstrates that cells in the anterior half of the tracheal pit are activated. In hh-mutant embryos migration of all tracheal branches is absent or stalled. These defects arise from a direct effect of Hh on tracheal cells, rather than by indirect effects on patterning of the ectoderm. Tracheal cell migration could be rescued by expressing Hh only in the tracheal cells, without rescuing the ectodermal defects. Signaling by several pathways, including the Hh pathway, thus serves to subdivide the uniform population of tracheal cells into distinct cell types that will subsequently be recruited into the different branches.

scholarly journals Dual regulation of lin28a by Myc is necessary during zebrafish retina regeneration

2019 ◽  
Vol 218 (2) ◽  
pp. 489-507 ◽  
Author(s):  
Soumitra Mitra ◽  
Poonam Sharma ◽  
Simran Kaur ◽  
Mohammad Anwar Khursheed ◽  
Shivangi Gupta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Therapeutic Intervention ◽  
Cellular Reprogramming ◽  
Retina Regeneration ◽  
Expression Of Genes ◽  
Mammalian Retina ◽  
Early Expression

Cellular reprogramming leading to induction of Muller glia–derived progenitor cells (MGPCs) with stem cell characteristics is essential for zebrafish retina regeneration. Although several regeneration-specific genes are characterized, the significance of MGPC-associated Mycb induction remains unknown. Here, we show that early expression of Mycb induces expression of genes like ascl1a, a known activator of lin28a in MGPCs. Notably, mycb is simultaneously activated by Ascl1a and repressed by Insm1a in regenerating retina. Here, we unravel a dual role of Mycb in lin28a expression, both as an activator through Ascl1a in MGPCs and a repressor in combination with Hdac1 in neighboring cells. Myc inhibition reduces the number of MGPCs and abolishes normal regeneration. Myc in collaboration with Hdac1 inhibits her4.1, an effector of Delta–Notch signaling. Further, we also show the repressive role of Delta–Notch signaling on lin28a expression in post-injured retina. Our studies reveal mechanistic understanding of Myc pathway during zebrafish retina regeneration, which could pave way for therapeutic intervention during mammalian retina regeneration.

Cells with affinity for periodic acid – Schiff are present in the pars intermedia of Atlantic salmon

1991 ◽  
Vol 69 (12) ◽  
pp. 3105-3108 ◽  
Author(s):  
Martin P. Komourdjian ◽  
Richard L. Saunders
Keyword(s):  
Atlantic Salmon ◽  
Periodic Acid ◽  
Cell Types ◽  
Point Of View ◽  
Pars Intermedia ◽  
Periodic Acid Schiff ◽  
Distinct Cell ◽  
Two Populations ◽  
Evolutionary Point

Examination of pituitaries from two populations of Atlantic salmon (Salmo salar) parr held under natural photoperiods revealed at least two histologically distinct cell types. One type has fine granules with affinity for lead hematoxylin (PIPbH). Another type, hitherto believed to be absent in salmonids, has larger granules which are Schiff-positive (PIPAS). These cells are significantly (P < 0.05) shorter and narrower and have significantly smaller nuclei (P < 0.05) than the PIPbH type. No evidence was found for ascribing to the PIPAS cells the functions assigned to them in other species: melanophore control and reproduction. However, PIPAS granules became evident only during fall-winter, when the smolting process begins. The incidence of these cells rose and then declined sharply during this period, suggesting a possible role in some aspect of smoltification. While the role of these PIPAS cells deserves further study, their presence is in itself important from an evolutionary point of view.

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