scholarly journals The homeobox gene, TGIF1, is required for chicken ovarian cortical development and generation of the juxtacortical medulla

Development ◽  
2021 ◽  
Author(s):  
Martin Andres Estermann ◽  
Claire Elizabeth Hirst ◽  
Andrew Thomas Major ◽  
Craig Allen Smith
Keyword(s):  
Granulosa Cells ◽  
Interstitial Cell ◽  
Cell Lineage ◽  
Homeobox Gene ◽  
Cell Types ◽  
Surface Epithelium ◽  
Cell Populations ◽  
Supporting Cells ◽  
Homeobox Transcription Factor ◽  
Steroidogenic Cells

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the homeobox transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in estrogen-mediated sex reversal experiments. Targeted mis-expression and gene knockdown indicate that TGIF1 is required, but not sufficient, for proper ovarian cortex formation. In addition, TGIF1 is identified as the first known regulator of juxtacortical medulla development. These findings provide new insights into chicken ovarian differentiation and development, specifically cortical and juxtacortical medulla formation.

scholarly journals TGIF1 is required for chicken ovarian cortical development and generation of the juxtacortical medulla

2021 ◽  
Author(s):  
Martin Andres Estermann ◽  
Claire E Hirst ◽  
Andrew T Major ◽  
Craig A Smith
Keyword(s):  
Granulosa Cells ◽  
Interstitial Cell ◽  
Ovarian Development ◽  
Cell Lineage ◽  
Cell Types ◽  
Surface Epithelium ◽  
Cell Populations ◽  
Supporting Cells ◽  
Over Expression ◽  
Steroidogenic Cells

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in sex reversal experiments. In addition, targeted over-expression and gene knockdown experiments indicate that TGIF1 is required for proper ovarian cortical formation. TGIF1 is identified as the first known regulator of juxtacortical medulla formation. These findings provide new insights into chicken ovarian differentiation and development, specifically in the process of cortical and juxtacortical medulla formation, a poorly understood area.

scholarly journals A Highly Active Homeobox Gene Promoter Regulated by Ets and Sp1 Family Members in Normal Granulosa Cells and Diverse Tumor Cell Types

2002 ◽  
Vol 277 (29) ◽  
pp. 26036-26045 ◽  
Author(s):  
Manjeet K. Rao ◽  
Sourindra Maiti ◽  
Honnavara N. Ananthaswamy ◽  
Miles F. Wilkinson
Keyword(s):  
Tumor Cell ◽  
Granulosa Cells ◽  
Family Members ◽  
Homeobox Gene ◽  
Gene Promoter ◽  
Cell Types ◽  
Highly Active

scholarly journals Enhancing Myocardial Repair with CardioClusters

2019 ◽  
Author(s):  
Megan M. Monsanto ◽  
Bingyan J. Wang ◽  
Zach R. Ehrenberg ◽  
Oscar Echeagaray ◽  
Kevin S. White ◽  
...  
Keyword(s):  
Interstitial Cell ◽  
Cell Types ◽  
Interstitial Cells ◽  
Neonatal Rat ◽  
Cellular Interaction ◽  
Cell Populations ◽  
Protective Effects ◽  
Next Generation ◽  
3D Microenvironment

AbstractBackgroundCellular therapy to treat heart failure is an ongoing focus of intense research and development, but progress has been frustratingly slow due to limitations of current approaches. Engineered augmentation of established cellular effectors overcomes impediments, enhancing reparative activity with improved outcomes relative to conventional techniques. Such ‘next generation’ implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, as previously reported by our group, prompted design of a three-dimensional (3D) structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell losses upon delivery.MethodsThree distinct populations of human cardiac interstitial cells including mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. Biological consequences of CardioCluster formation were assessed by multiple assays including single cells RNA-Seq transcriptional profiling. Protective effects of CardioClusters in vitro were measured using cell culture models for oxidative stress and myocardial ischemia in combination with freshly isolated neonatal rat ventricular myocytes. Long-term impact of adoptively transferred CardioClusters upon myocardial structure and function in a xenogenic model of acute infarction using NODscid mice was assessed over a longitudinal time course of 20-weeks.ResultsCardioCluster design enables control over composite cell types, cell ratios, size, and preservation of structural integrity during delivery. Profound changes for biological properties of CardioClusters relative to constituent parental cell populations include enhanced expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines. The CardioCluster 3D microenvironment maximizes cellular interaction while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster delivery improves cell retention following intramyocardial injection with preservation of long-term cardiac function relative to monolayer-cultured cells when tested in an experimental murine infarction model followed for up to 20 weeks post-challenge. CardioCluster-treated hearts show increases in capillary density, preservation of cardiomyocyte size, and reduced scar size indicative of blunting pathologic infarction injury.ConclusionsCardioClusters are a novel ‘next generation’ development and delivery approach for cellular therapeutics that potentiate beneficial activity and enhance protective effects of human cardiac interstitial cell mixed populations. CardioClusters utilization in this preclinical setting establishes fundamental methodologic and biologic insights, laying the framework for optimization of CardioCluster design to provide greater efficacy in cell-based therapeutic interventions intended to mitigate cardiomyopathic damage.

107 Localization of Kisspeptin Immunoreactivity in the Cat Ovary on Different Reproductive Stages

2018 ◽  
Vol 30 (1) ◽  
pp. 193
Author(s):  
P. Tanyapanyachon ◽  
O. Amelkina ◽  
K. Chatdarong
Keyword(s):  
Corpus Luteum ◽  
Granulosa Cells ◽  
Ovarian Surface Epithelium ◽  
Domestic Cat ◽  
Primary Antibody ◽  
Surface Epithelium ◽  
Domestic Cats ◽  
Luteal Cells ◽  
Theca Cells ◽  
Steroidogenic Cells

Kisspeptin (Kp) is considered one of the main regulators of the reproductive axis, exerting its effects via stimulating GnRH expression in the hypothalamus. Apart from its central localization in the hypothalamus, the presence of Kp has been reported in the ovary, with possible local function. To date, very little is known about the ovarian Kp in the domestic cat. Therefore, our aim was to investigate the presence and localization of Kp at different reproductive stages in domestic cat ovaries. Twenty ovaries were collected from free-ranging domestic cats (body weight 2.7–4.5 kg) after routine ovariohysterectomy. Reproductive stages were classified by ovarian gross morphology, vaginal cytology, and blood progesterone level. Ovarian samples were grouped into inactive (n = 6), follicular (n = 8), and luteal stages (n = 6). Tissues were fixed in 4% paraformaldehyde and processed routinely. Immunohistochemistry was performed using polyclonal rabbit Kp-10 primary antibody (AB9754; Millipore, Billerica, MA, USA) at 1:500 at 4°C overnight. Immunoreactive cells were identified by avidin-biotin-peroxidase system. Rat hypothalamic tissue was used as a positive control. Primary antibody was substituted with PBS and normal rabbit IgG as the negative and isotypic negative controls, respectively. In addition, primary antibody was incubated with metastin overnight and applied for preabsorption test. Negative, isotypic negative, and preabsorption tests showed no staining. Immunoreactive Kp was detected in the ovaries of all reproductive stages with no obvious changes in localization or intensity of staining between stages. Kisspeptin was present in the cytoplasm of oocytes, granulosa cells, and theca cells of preantral (primordial, primary, and secondary) follicles and antral follicles. Interestingly, in most follicles, Kp staining was more prominent in theca cells and oocytes compared with granulosa cells. In corpus luteum, Kp was localised in the cytoplasm of luteal cells, with more intense staining on the periphery of corpus luteum compared with the middle in 3 luteal samples, whereas the rest of the samples demonstrated homogeneous staining distribution. Apart from oocytes and steroidogenic cells, Kp was also present in the cytoplasm of cells of the ovarian surface epithelium. Our study for the first time demonstrated the presence and localization of Kp in the ovary of the domestic cats. The localization of Kp in the cat oocyte is similar to previous reports on hamsters and dogs, indicating a possible function in oocyte development. The staining in steroidogenic cells, mainly theca cells and luteal cells, is in good agreement with studies on hamsters, rats, humans, and marmosets, suggesting the possible local involvement of Kp in steroidogenesis. In addition, Kp staining in the ovarian surface epithelium suggests a possible role in the ovarian remodeling after ovulatory defects, as reported in humans and marmosets. This research was funded by the RGJ PhD program PHD/01882556; RG 7/2559.

Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development

Development ◽  
1996 ◽  
Vol 122 (10) ◽  
pp. 3013-3021 ◽  
Author(s):  
J. Partanen ◽  
M.C. Puri ◽  
L. Schwartz ◽  
K.D. Fischer ◽  
A. Bernstein ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Late Phase ◽  
Cell Lineage ◽  
Cell Types ◽  
Limb Bud ◽  
Cell Populations ◽  
Cell Integrity

TIE is a receptor tyrosine kinase expressed in both mature endothelial cells and their precursors, as well as in some hematopoietic cells. Mouse embryos homozygous for a disrupted Tie allele die at midgestation due to impaired endothelial cell integrity and resulting hemorrhage. Here we have performed chimeric analysis to study further the function of the murine TIE in the development of embryonic vasculature and in the hematopoietic system. Cells lacking a functional Tie gene (tie(lcz)/tie(lczn-) cells) contributed to the embryonic vasculature at E10.5 as efficiently as cells heterozygous for a targeted Tie allele (tie(lcz)/+ cells). Thus, TIE does not play a significant role in vasculogenesis or in early angiogenic processes, such as formation of the intersomitic arteries and limb bud vascularization. At E15.5 tie(lcz)/tie(lczn-) cells still readily contributed to major blood vessels and to endothelial cells of organs such as lung and heart, which have been suggested to be vascularized by angioblast differentiation. In contrast, the tie(lcz)/tie(lczn-) cells were selected against in the capillary plexuses of several angiogenically vascularized tissues, such as brain and kidney. Our results thus support a role for TIE in late phases of angiogenesis but not vasculogenesis. Furthermore, the results suggest that different mechanisms regulate early and late angiogenesis and provide support for a model of differential organ vascularization by vasculogenic or angiogenic processes. Analysis of adult chimeras suggested that TIE is required to support the survival or proliferation of certain types of endothelial cells demonstrating heterogeneity in the growth/survival factor requirements in various endothelial cell populations. Chimeric analysis of adult hematopoietic cell populations, including peripheral platelets and bone marrow progenitor cells, revealed that tie(lcz)/tie(lczn-) cells were able to contribute to these cell types in a way indistinguishable from tie(lcz)/+ or wild-type cells. Thus, the primary function of TIE appears to be restricted to the endothelial cell lineage.

scholarly journals Oestrogen receptor α and β, androgen receptor and progesterone receptor mRNA and protein localisation within the developing ovary and in small growing follicles of sheep

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Jennifer L Juengel ◽  
Derek A Heath ◽  
Laurel D Quirke ◽  
Kenneth P McNatty
Keyword(s):  
Granulosa Cells ◽  
Ovarian Development ◽  
Cell Types ◽  
Surface Epithelium ◽  
Fetal Life ◽  
Follicular Growth ◽  
Early Stages ◽  
Thecal Cells ◽  
Protein Localisation ◽  
Type 3

A first step to elucidating the roles that steroids may play in the processes of ovarian development and early follicular growth is to identify the cell types that are likely to be receptive to steroids. Thus, cell types expressing receptors for oestrogen (α and β form; ERα and ERβ respectively), androgen (AR) and progesterone (PR) were determined by in situ hybridisation and immunohistochemistry in ovine ovarian tissues collected during ovarian development and follicular formation (days 26–75 of fetal life) as well as during the early stages of follicular growth. Expression of ERβ was observed early during ovarian development and continued to be expressed throughout follicular formation and also during the early stages of follicular growth. ERβ was identified in germ cells as well as in the granulosa cells. At the large preantral stage of follicular growth, expression of ERα was also consistently observed in granulosa cells. AR was first consistently observed at day 55 of fetal life in stroma cells throughout the ovary. Within the follicle, expression was observed in granulosa and thecal cells from the type-2 to -3 stage of follicular growth. PR mRNA did not appear to be expressed during ovarian development (days 26–75 of gestation). However, PR (mRNA and protein) was observed in the theca of type-3 (small preantral) and larger follicles, with mRNA – but not protein – observed in granulosa cells of some type-4 and 5 follicles. Expression of ERβ, ERα and AR, as well as PR, was also observed in the surface epithelium and ovarian stroma of the fetal, neonatal and adult ovary. Thus, in sheep, steroid hormones have the potential to regulate the function of a number of different ovarian cell types during development, follicular formation and early follicular growth.

194 EPIGENETIC REMODELING OF ADULT SOMATIC CELLS

2014 ◽  
Vol 26 (1) ◽  
pp. 211 ◽  
Author(s):  
G. Pennarossa ◽  
S. Maffei ◽  
F. Gandolfi ◽  
T. A. L. Brevini
Keyword(s):  
Granulosa Cells ◽  
Muscle Development ◽  
Morphological Changes ◽  
Primary Cultures ◽  
Cell Lineage ◽  
Cell Types ◽  
Plastic State ◽  
Specific Marker ◽  
Germ Layer

Mammalian differentiation is obtained through epigenetic regulations that shape the genome, which is identical in all cells, to distinct phenotypes and tissue specific identities. The differentiated state of mature cells in an adult organism is therefore acquired through epigenetic restrictions that lead to a gradual loss of differentiative potency. In agreement with this, recent experiments demonstrate that terminally differentiated cells can be induced to de-differentiate in vitro and increase their plasticity in response to epigenetic modifiers that are capable of reverting cells from their lineage commitment to a more plastic state. Here we describe experiments where we prepared porcine skin fibroblasts and granulosa primary cultures and exposed them to an inhibitor of DNA methylation, the 5-aza-cytidine (5-aza-CR), to increase cell plasticity. Taking advantage of the obtained increased permissivity window, we investigated the ability of 5-aza-CR treated cells to respond to specific differentiation conditions and be re-addressed to a different cell lineage either within the same germ layer or to a different germ layer. Cells were evaluated for their morphological changes and assessed using RT-PCR and immunocytochemical studies during the treatment. Following the exposure to 5-aza-CR the phenotype of both cell types changed. Treated cells displayed an oval or round shape, and appeared smaller with larger nuclei and granular and vacuolated cytoplasm. This was accompanied by an active expression of the main pluripotency-related genes OCT4, NANOG, SOX2, and REX1, originally undetectable in untreated fibroblasts and granulosa cells. 5-aza-CR treated granulosa cells cultured with recombinant human vascular endothelial growth factor to induce myogenic specification (different lineage within the same germ layer) suppressed the expression of granulosa specific marker (Cytokeratin) as well as of the pluripotency genes, and expressed MYOD, MYF5, and MYOG (earliest myogenic markers that are involved in the coordination of skeletal muscle development or myogenesis). In order to trans-differente 5-aza-CR treated fibroblasts to cells of a different germ layer, they were exposed to activin A to promote endoderm commitment. Cells down-regulated Vimentin (fibroblast marker) as well as pluripotent gene expression and transcribed Nestin (transiently involved in multi-lineage progenitor cell differentiation), SOX17, FOXA2 (induction of definitive endoderm), and HNF4A, HNF1 (primitive gut tube specific genes). Altogether these results suggest that it is possible to obtain a direct inter-lineage conversion by removing epigenetic restriction, using demethylating agents such as 5-aza-CR, and avoiding a stable pluripotent state. This novel approach may represent a promising tool for regenerative medicine because it does not involve the use of any transgenic modifications, retroviral transfection, or both. Supported by Network Lombardo iPS (NetLiPS) Project ID 30190629.

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

scholarly journals Stomatal Development in the Context of Epidermal Tissues

2021 ◽  
Author(s):  
Keiko U Torii
Keyword(s):  
Arabidopsis Thaliana ◽  
Molecular Genetic ◽  
Cell Lineage ◽  
Optimal Growth ◽  
Cell Types ◽  
State Transitions ◽  
Stomatal Development ◽  
Water Control ◽  
Pavement Cells ◽  
The Core

Abstract Background Stomata are adjustable pores on the surface of plant shoots for efficient gas exchange and water control. The presence of stomata is essential for plant growth and survival, and the evolution of stomata is considered as a key developmental innovation of the land plants, allowing colonization on land from aquatic environments some 450 million years ago. In the past two decades, molecular genetic studies using the model plant Arabidopsis thaliana identified key genes and signalling modules that regulate stomatal development: master-regulatory transcription factors that orchestrate cell-state transitions and peptide-receptor signal transduction pathways, which, together, enforce proper patterning of stomata within the epidermis. Studies in diverse plant species, ranging from bryophytes to angiosperm grasses, have begun to unravel the conservation and uniqueness of the core modules in stomatal development. Scope Here, I review the mechanisms of stomatal development in the context of epidermal tissue patterning. First, I introduce the core regulatory mechanisms of stomatal patterning and differentiation in the model species Arabidopsis thaliana. Subsequently, experimental evidence is presented supporting the idea that different cell types within the leaf epidermis, namely stomata, hydathodes pores, pavement cells, and trichomes, either share developmental origins or mutually influence each other’s gene regulatory circuits during development. Emphasis is taken on extrinsic and intrinsic signals regulating the balance between stomata and pavement cells, specifically by controlling the fate of Stomatal-Lineage Ground Cells (SLGCs) to remain within the stomatal-cell lineage or differentiate into pavement cells. Finally, I discuss the influence of inter-tissue-layer communication between the epidermis and underlying mesophyll/vascular tissues on stomatal differentiation. Understanding the dynamic behaviors of stomatal precursor cells and their differentiation in the broader context of tissue and organ development may help design plants tailored for optimal growth and productivity in specific agricultural applications and a changing environment.

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