Browsing by Author "Cross, James C."
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- ItemOpen AccessActivin Is a Local Regulator of Human Cytotrophoblast Cell Differentiation(The Endocrine Society, 1997-09) Caniggia, Isabella; Lye, Stephen J.; Cross, James C.
- ItemOpen AccessAdaptability and Function of the Placental Endocrine System(2020-06-08) Eaton, Malcolm Ellis; Cross, James C.; Hallgrímsson, Benedikt; De Bruyn, Raylene; Pittman, Quentin J.; Slater, Donna M.; Davidge, Sandra ThomasThe placenta acts as the arbitrator for the exchange of nutrients and gases across the feto-maternal interface, ensuring that the fetus can grow, and the mother can remain healthy to deliver and nurture her offspring. The placenta achieves this by changing its structure and function throughout gestation. Failure to undergo these changes is a major cause of obstetric syndromes, intrauterine growth restriction and pre-term birth. These complications result in deleterious long-term outcomes for both fetus and mother and understanding the complex aetiology of these complications is fundamental to impacting lifelong health. One of the less well-studied ways that the placenta adapts is by secreting hormones that regulate maternal adaptations to pregnancy. Previous work in the Cross lab established that a family of 22 Prolactin-related hormone genes, termed the placenta Prolactin-related hormones (PPRH), that are specifically expressed from the mouse placenta regulate maternal adaptations to pregnancy. The mouse provided a model to study how the placenta adapted its structure and function to changes in the maternal environmental and PPRH levels. We first established the normal course of cell growth in the placenta to understand the timing of changes in trophoblast cells number and found evidence of cell hypertrophy and endoreduplication in addition to hyperplasia. We then challenged pregnancies with a maternal diet low in protein. We found that the normal course of cellular differentiation and growth was altered, but that these changes were adapting to preserve fetal growth. Interestingly, we found that male and female fetuses used different strategies. We then created a model that was haplo-deficient in PPRH genes and, to our surprise, fetuses were overgrown while mothers failed to gain weight late-term. Interpreting the expression patterns of individual hormone genes in the context of other placental knockouts helped us identify putative roles for several hormones and demonstrated that this locus is highly adaptable. Distinguishing the targets and functions of these hormones and separating between primary and secondary effects remains a topic of interest. In examining PPRH null mutants, we found that the size of the maternal liver, spleen and gut were altered, along with the gut microbiota. These results indicate that the placenta is a highly adaptable organ that changes in normal pregnancy and has mechanisms built in to mitigate impacts of environmental changes. By studying the changes over time, we reveal insights into how placenta-specific hormones regulate maternal physiology, placental function and fetal growth outcomes. There is still a great deal to learn about the placenta but increasing our understanding of this fascinating organ will contribute to the interpretation and treatment of obstetric syndromes.
- ItemOpen AccessInterferon-Stimulated Gene-15 (Isg15) Expression Is Up-Regulated in the Mouse Uterus in Response to the Implanting Conceptus(The Endocrine Society, 2003-07) Austin, Kathy J.; Bany, Brent M.; Belden, E. Lee; Rempel, Lea A.; Cross, James C.; Hansen, Thomas R.
- ItemEmbargoInvestigating the mechanisms underlying age-related dysfunctions in skin and hair follicle regeneration(2020-05-29) Shin, Wisoo; Biernaskie, Jeff A.; Huang, Peng; Cross, James C.; Cobb, John A.Age-associated decline in overall skin function and impaired cutaneous wound healing are both direct consequences of the progressively weakening dermis and degeneration of necessary appendages such as glands, nerves and hair follicles (HFs). With a fresh perspective and access to new tools, I revisit aging skin phenotypes including hair loss and deficiency in wound healing from the perspective of the mesenchyme and its progenitors. In Chapter 2, I present a manuscript establishing the transcriptomic identities of bipotent hair follicle mesenchymal stem cells (hfDSCs) and its progeny dermal papilla (DP) via bulk RNA sequencing. Utilizing in vitro cell culture drug treatments, in vivo drug injections, and genetic deletion of Rspondin3 (Rspo3), my work define Rspo3 as an important modulator of epithelial-mesenchymal crosstalk in HF regeneration. In Chapter 3, I ask whether hfDSCs are lost with age and whether their dysfunction contributes to age-associated hair loss. Reporter mice experiments including long-term fate mapping and in vivo clonal analysis characterize the functional deficits of hfDSCs. Analysis of single-cell RNA sequencing (scRNAseq) data reveals that the driver of HF mesenchymal aging is senescence. In Chapter 4, I present on going work that describes the failure of aged mice to undergo wound induced hair neogenesis (WIHN). Using scRNAseq, I determine that mesenchymal fibroblasts in aged mice cannot acquire a regenerative phenotype after injury due to an overabundance of senescent fibroblasts. Senescent fibroblasts persist into late stages of wound healing, contributing to the loss of WIHN. In Chapter 5, I present a co-lead study investigating the impact of genomic instability on progenitor maintenance. I introduce a novel model of accelerated aging with skin deficiencies such as hair loss and hyper pigmentation. Genomic instability significantly impairs the HF regeneration cycle, and as a result, the HF degenerates in a process closely resembling natural HF aging. Characterizing the roles of aging dermal progenitors in skin deficiencies provides new insights into skin aging and aging stem cell research. Additionally, my work on defining functionally diverse fibroblast populations contribute to the growing appreciation for the importance of fibroblast heterogeneity in maintaining overall skin function.
- ItemOpen AccessMultiple Regulatory Elements Are Required to Direct Trophoblast Interferon Gene Expression in Choriocarcinoma Cells and Trophectoderm(The Endocrine Society, 1994-04) Leaman, Douglas W.; Cross, James C.; Roberts, Michael R.
- ItemOpen AccessPeriodic Expression of the Cyclin-dependent Kinase Inhibitor p57Kip2 in Trophoblast Giant Cells Defines a G2-like Gap Phase of the Endocycle(American Society for Cell Biology, 2000-03) Hattori, Naka; Davies, Tyler C.; Anson-Cartwright, Lynn; Cross, James C.
- ItemOpen AccessPlacental cell lineage tracing using cre recombinase transgenic mice(2005) Fortier, Amanda Lea; Cross, James C.
- ItemOpen AccessThe Production, Purification, and Bioactivity of Recombinant Bovine Trophoblast Protein-1 (Bovine Trophoblast Interferon)(The Endocrine Society, 1990-10) Klemann, Stephen W.; Li, Junzhi; Imakawa, Kazuhiko; Cross, James C.; Francis, Harriet; Roberts, Michael R.
- ItemOpen AccessProlactin Receptor Is Required for Normal Glucose Homeostasis and Modulation of β-Cell Mass during Pregnancy(The Endocrine Society, 2009-04) Huang, Carol; Snider, Francis; Cross, James C.
- ItemOpen AccessReprogramming the Cell Cycle for Endoreduplication in Rodent Trophoblast Cells(American Society for Cell Biology, 1998-04) MacAuley, Alasdair; Cross, James C.; Werb, Zena
- ItemOpen AccessRole of autophagy in porcine spermatogonia(2018-08-07) Valenzuela-Leon, Paula; Dobrinski, Ina; Cross, James C.; Van Der Hoorn, Frans A.; Wynne-Edwards, Katherine ElizabethSpermatogonial stem cells (SSCs) sustain spermatogenesis through tightly controlled self renewal and differentiation processes. A long-term culture for porcine spermatogonia has not been established yet. To thrive in culture conditions, a cell requires to adapt to the environment. One of the tools that cells have developed to manage stress is autophagy. Autophagy is induced by cellular stress, which results in lysosomal degradation and recycling of the degradation product to generate energy for cellular homeostasis. Therefore, the main objective of this thesis is to elucidate the role autophagy plays in porcine germ cells. Initially, we identified that autophagy is active at basal levels in situ; upon isolation from the testis, the levels of autophagy increase significantly. Autophagic levels were then analyzed in testis tissue formed de novo. After 6 weeks, autophagic levels were at basal levels, which indicated that re-introduction to the microenvironment decreases germ cell stress. Considering that in vitro conditions upregulate autophagy, germ cells were cultured in two different media, and found that levels of autophagy are lower in nutrient rich medium. Levels of reactive oxygen species (ROS) were measured and were found to decrease germ cell viability; upon autophagy stimulation, viability increased. Conversely, upon autophagic inhibition, ROS increased, and germ cell viability decreased. These results suggested that autophagy is a cytoprotective mechanism for germ cells and can be used as an indicator for stress in vitro. To investigate the role of autophagy in germ cells in the presence of toxicants, we evaluated the levels of autophagy in primate testis tissue xenografted to mice exposed to phthalates. It was found that germ cells exposed to this toxicant had higher levels of autophagy than the controls. To evaluate the effects of toxicants in vitro, germ cells were treated with another phthalate, which caused germ cell viability to decrease. Upon autophagy induction, germ cell viability increased accordingly. These results show that autophagy is a cell protective mechanism for germ cells exposed to a toxicant. Overall, the work in this thesis identifies autophagy as an essential process for germ cell homeostasis.
- ItemOpen AccessSpatial and temporal expression of the 23 murine Prolactin/Placental Lactogen-related genes is not associated with their position in the locus(BioMed Central, 2008-07-28) Simmons, David G; Rawn, Saara; Davies, Alastair; Hughes, Martha; Cross, James C.
- ItemOpen AccessThe function of prolactin family genes in murine pregnancy(2010) Rawn, Saara Mirjam; Cross, James C.
- ItemOpen AccessThe role of Hic1 in testicular smooth muscle cells(2018-09-21) Uchida, Aya; Dobrinski, Ina; Klein, C.; Cross, James C.Testicular smooth muscle cells, including peritubular myoid cells and vasculature smooth muscle cells, regulate spermatogonial stem cell function in the mammalian testis. However, the mechanisms and signaling pathways that affect germ cell function largely remain to be elucidated. Here we report the expression of Hypermethylated in cancer 1 (Hic1) in testicular smooth muscle cells by using the Hic1CreERT2:RosatdTomato mice. Linage tracing experiments with Hic1CreERT2:RosatdTomato mice revealed that Hic1 expressing peritubular myoid expanded their population throughout testicular development. We hypothesized that Hic1 expression in testicular smooth muscle cells is involved in maintenance of spermatogenesis and tested this hypothesis by using aSMACreERT2:Hic1flox:RosatdTomato mice that allow conditional knock out (cKO) of Hic1 in smooth muscle cells. Deletion of Hic1 in smooth muscle cells resulted in aberrant spermatogenesis with degenerate seminiferous epithelium and dilated seminiferous tubules in mouse testis. The Hic1 cKO mice had heavier testes with more undifferentiated spermatogonia and fewer differentiated germ cells compared to controls. The peritubular myoid cells surrounding the seminiferous tubules were distributed at similar density in cKO and control mice, yet the number of Sertoli cells per seminiferous tubule in cKO mice was decreased compared to the control mice. Deposition of fibronectin, an extracellular matrix protein secreted from peritubular myoid cells, was disrupted in Hic1 cKO mice, suggesting a functional defect in Hic1 cKO peritubular myoid cells. Additionally, a tight junction protein, occludin, showed a disruption in cKO mice, indicating an indirect effect of cKO peritubular myoid cells on the germ cells, through Sertoli cells. Taken together, we demonstrated that Hic1 signaling in testicular myoid cells is playing an important role to regulate spermatogenesis. This study demonstrated the expression of Hic1 in testicular smooth muscle cells and provided insights into a signaling pathway in testicular smooth muscle cells to directly/indirectly affect germ cells.
- ItemOpen AccessThe Role of the Mrj Co-chaperone During Early Mouse Embryonic Development(2008) Watson, Erica Danielle; Cross, James C.
- ItemOpen AccessTranscription Factors Underlying the Development and Endocrine Functions of the Placenta(The Endocrine Society, 2002) Cross, James C.; Anson-Cartwright, Lynn; Scott, Ian C.
- ItemOpen AccessTranscriptional regulation of the Hand I gene in the developing mouse conceptus(2007) Rourke-Sim, Dana Rae; Cross, James C.