Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures

• Published in: Cell reports (Cambridge) Vol. 32; no. 6; p. 108027
• Main Authors: Man, Limor, Lustgarten-Guahmich, Nicole, Kallinos, Eleni, Redhead-Laconte, Zachary, Liu, Sally, Schattman, Benjamin, Redmond, David, Hancock, Kolbe, Zaninovic, Nikica, Schattman, Glenn, Rosenwaks, Zev, James, Daylon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.08.2020; Elsevier
• Subjects: antral follicle; fertility preservation; granulosa cell; human folliculogenesis; ovarian tissue transplantation; ovarian tissue xenograft; single-cell RNA sequencing; theca cell; single-cell RNA sequencing; ovarian tissue xenograft; antral follicle; human folliculogenesis; theca cell; fertility preservation; ovarian tissue transplantation; granulosa cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108027

The activation, growth, and maturation of oocytes to an ovulatory phase, termed folliculogenesis, is governed by the orchestrated activity of multiple specialized cell types within the ovary; yet, the mechanisms governing diversification and behavior of discrete cellular sub-populations within follicles are poorly understood. We use bulk and single-cell RNA sequencing to distinguish the transcriptional signature of prospectively isolated granulosa and theca/stroma cell subsets within human antral follicles derived from xenografts or ovaries. The analysis deconstructs phenotypic diversification within small (<4 mm) antral follicles, identifying secreted factors that are differentially enriched between mural and oophorus granulosa cells, and segregating stromal/support and steroidal activity between theca externa and interna, respectively. Multiple factors are differentially expressed in follicles of xenograft versus ovarian origin. These data capture a high-resolution transcriptional signature of granulosa and theca subpopulations and provide a systems-level portrait of cellular diversification in early antral human follicles. [Display omitted] •Labeling and sorting of granulosa and theca/stroma subsets in human ovarian follicles•PVRL1 distinguishes the oophorus compartment of antral-stage follicles•scRNA-seq indicates atypical molecular signature of granulosa cells within xenografts•Analysis of theca/stroma subsets reveals heterogeneity and differentiation hierarchy Man et al. establish robust methods for prospective isolation of effector cell subsets that mediate the growth and maturation of oocytes within ovarian follicles and apply these methods to elucidate transcriptional heterogeneity that is uniquely associated with cells derived from xenografted versus native ovarian tissue.