ABSTRACT
Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells.
Subject(s)
Fibroblast Growth Factors/metabolism , Pluripotent Stem Cells/cytology , Somatomedins/metabolism , Cell Culture Techniques , Cell Line , Cell Proliferation , Culture Media, Conditioned/chemistry , Fibroblast Growth Factors/pharmacology , Gene Expression Regulation , Humans , Insulin-Like Growth Factor II/biosynthesis , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/pharmacology , Pluripotent Stem Cells/drug effects , Pluripotent Stem Cells/metabolism , Proteome/metabolism , Receptor, IGF Type 1/deficiency , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , Signal Transduction/drug effects , Somatomedins/biosynthesis , Somatomedins/pharmacology , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/pharmacologyABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARSCov- 2) is hypothesized to have originated from a spillover event from an animal reservoir. This has raised many questions, with an important one being whether the widely disseminated coronavirus disease 2019 (COVID-19) is transmissible to other animal species. SARS-CoV-2 is primarily transmitted person to person. K9-to-human transmission, although theoretically possible via fomites, is considered minimal, if at all, and there have been no reported cases of K9-to-human transmission. Human-to-K9 transmission, although rare, seems more likely; however, in only one case has a K9 been suspected to have displayed symptoms of COVID-19. Preparation, decontamination, hand hygiene, and distancing remain the key factors in reducing transmission of the virus. The information presented is applicable to personnel operating within the military conventional and Special Operation Forces as well as civilian Tactical Emergency Medical Services communities who may have the responsibility of supporting an operational K9.