Biology subjects

Hamidzada, H.

Publications and source records attributed to Hamidzada, H..

3 recordsLinked to original sources

bioRxiv2023

Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells

Abstract (Summary) Cardiac fibroblasts play an essential role in the development of the heart and have been implicated in disease progression in the context of fibrosis and regeneration. Here, we established a simple organoid culture platform using human pluripotent stem cell-derived epicardial cells and ventricular cardiomyocytes to study cardiac fibroblasts development, maturation and heterogeneity under normal conditions and following treatment with pathological stimuli. We demonstrated that this system models the early interactions between epicardial cells and cardiomyocytes to generate a population of fibroblasts that recapitulates many aspects of fibroblast behaviour in vivo including changes associated with maturation and in response to pathological stimuli associated with cardiac injury. Using single cell transcriptomics, we show that the hPSC-derived organoid fibroblast population displays a high degree of heterogeneity that approximates the heterogeneity of populations in both the normal and diseased human heart. Additionally, we identified a unique subpopulation of fibroblasts possessing reparative features previously characterized in the hearts of model organisms. Taken together, our system recapitulates many aspects of human cardiac fibroblast specification, development and maturation providing a platform to investigate the role of these cells in human cardiovascular development and disease.

cell biology↗

bioRxiv2023

Knockout of endoplasmic reticulum localized molecular chaperone HSP90.7 impairs seeding development and cellular auxin homeostasis in Arabidopsis

The Arabidopsis endoplasmic reticulum localized heat shock protein HSP90.7 modulates tissue differentiation and stress responses; however, complete knockout lines have not been previously reported. In this study, we identified and analyzed a mutant allele, hsp90.7-1, which did not express any protein and showed seedling lethality. Microscopic analyses revealed its essential role in male and female fertility, trichomes and root hairs development, proper chloroplast function, and in apical meristem maintenance and differentiation. Comparative transcriptome and proteome analyses also revealed a role of the protein in a multitude of cellular processes. Particularly, the auxin responsive pathway was specifically down-regulated in the hsp90.7-1 mutant seedlings. We measured a much-reduced auxin content in both root and shoot tissues. Through comprehensive histological and molecular analyses, we demonstrated PIN1 and PIN5 expressions were dramatically reduced in the mutant, and the TAA-YUCCA primary auxin biosynthesis pathway was also down-regulated, thus revealing a critical new role of HSP90.7 in the regulation of auxin responses. This study therefore not only fulfilled a gap in understanding the essential role of HSP90 paralogs in eukaryotes, but also provided a mechanistic insight on this molecular chaperone in regulating plant growth and development via modulating cellular auxin homeostasis.

plant biology↗

bioRxiv2022

Microbial Energy Metabolism Fuels a CSF2-dependent Intestinal Macrophage Niche within Tertiary Lymphoid Organs

Maintaining intestinal macrophage (MP) heterogeneity is critical to ensure tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically shape colonic MP development, although there remains a fundamental gap in our understanding of the details of such collaboration. Here, we report tertiary lymphoid organs (TLOs), enriched in group 3 innate lymphoid cells (ILC3s), as a microbiota-operated intestinal niche for the development of monocyte-derived MPs. ILC3-derived colony stimulating factor 2 (CSF2) serves as a developmental and functional determinant for MPs and required microbe-derived extracellular adenosine 5-triphosphate (ATP) as a trigger. Microbial communities rich in extracellular ATP promoted MP turnover via ILC3 activity in an NLRP3-dependent fashion. Single cell RNA-sequencing of MPs revealed unique TLO-associated, CSF2-dependent MP populations critical for anti-microbial defense against enteric infection. Collectively, these findings describe a fundamental framework that constitutes an intestinal MP niche fueled by microbial energy metabolism.

immunology↗