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Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [single cell RNA-seq]

ABSTRACT: Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [single cell RNA-seq]

PROVIDER: PRJNA674385 | ENA |

REPOSITORIES: ENA

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	SRR12975289.fastq.gz	Fastqsanger.gz

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Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [bulkRNAseq]

Project description:Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [bulkRNAseq]

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Single-cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium.

Project description:The endometrium is a dynamic tissue that exhibits remarkable resilience to repeated episodes of differentiation, breakdown, regeneration, and remodeling. Endometrial physiology relies on a complex interplay between the stromal and epithelial compartments with the former containing a mixture of fibroblasts, vascular, and immune cells. There is evidence for rare populations of putative mesenchymal progenitor cells located in the perivascular niche of human endometrium, but the existence of an equivalent cell population in mouse is unclear. We used the Pdgfrb-BAC-eGFP transgenic reporter mouse in combination with bulk and single-cell RNA sequencing to redefine the endometrial mesenchyme. In contrast to previous reports we show that CD146 is expressed in both PDGFRβ + perivascular cells and CD31 + endothelial cells. Bulk RNAseq revealed cells in the perivascular niche which express the high levels of Pdgfrb as well as genes previously identified in pericytes and/or vascular smooth muscle cells (Acta2, Myh11, Olfr78, Cspg4, Rgs4, Rgs5, Kcnj8, and Abcc9). scRNA-seq identified five subpopulations of cells including closely related pericytes/vascular smooth muscle cells and three subpopulations of fibroblasts. All three fibroblast populations were PDGFRα+/CD34 + but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively. Immunohistochemistry was used to investigate the spatial distribution of these populations revealing F1/NGFR + cells in most abundance beside epithelial cells. We provide the first definitive analysis of mesenchymal cells in the adult mouse endometrium identifying five subpopulations providing a platform for comparisons between mesenchymal cells in endometrium and other adult tissues which are prone to fibrosis.

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Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [bulkRNAseq]

Project description:The goal of this study was to generate an NGS-derived transcriptome profile (RNA-seq) for a population of perivascular mesenchymal cells from healthy cycling Pdgfrb-BAC-eGFP mouse uterus. Bulk RNAseq revealed cells in the perivascular niche which express high levels of Pdgfrb (GFPhigh) also express genes previously identified in pericytes and/or vascular smooth muscle cells including Acta2, Myh11, Olfr78, Cspg4, Rgs4, Rgs5, Kcnj8 and Abcc9. Our work uncovers novel target genes for perivascular cell populations in mouse endometrium providing a platform to understand the role of these cells in endometrial physiology and disease.

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Project description:The human menstrual cycle can be divided into two major phases by the event of ovulation. Before ovulation, in the proliferative or follicular phase, the endometrium proliferates under the influence of estradiol produced by growing ovarian follicles. After ovulation, in the secretory or luteal phase, ovarian progesterone produced by the newly formed corpus luteum drives a process of differentiation during which the endometrium becomes competent to receive and support the growth of the embryo. Single-cell analyses at the RNA level from our group and others have begun to decipher cell-type specific expression in the endometrium. How these events are controlled at the chromatin level remains elusive, however. In this study, we applied single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) to profile the epigenetic landscapes of human endometrial samples across the menstrual cycle.

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Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [single cell RNA-seq]

Project description:We profile the transcriptomes of over 5,000 mouse single cells, yielding molecular definitions for mesenchymal cell types present in heathy cycling mouse uterus. We uncover novel heterogeneity within the Pdgfrb+ mesenchymal cell compartment of the mouse uterus, defining five subpopulations including two closely related Cspg4+ pericytes/vascular smooth muscle cells and three Pdgfra+Cd34+ subpopulations of fibroblasts.Our work dissects cellular heterogeneity within the mouse uterine mesenchyme providing a platform to understand the roles of these cell populations in uterine physiology and disease and for comparisons between mesenchymal cells in endometirum and other adult tissue which are prone to fibrosis.

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Single-cell RNA sequencing of human endometrium across the luteal phase of the menstrual cycle

Project description:The fate of the human endometrium is determined during the mid-luteal window of implantation, a crucial period when endometrial stromal cells (EnSCs) differentiate into specialized decidual cells. Upon embryo implantation, these differentiating EnSCs transform the endometrium into the decidua of pregnancy. Conversely, in the absence of pregnancy, decreasing progesterone levels trigger tissue breakdown, leading to menstruation. Despite our understanding of these processes, the precise mechanisms governing this tissue transformation remain elusive. To bridge this knowledge gap, we conducted single-cell RNA sequencing, mapping the transcriptomic profiles of timed endometrial biopsies throughout the luteal phase of the menstrual cycle.

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