Balzamo, Chiara (2024) Identification of stem cell-specific markers for the molecular characterization of human Adult Gastric Stem Cells (hAGSCs). [Tesi di dottorato]

	Testo BALZAMO_Chiara_36_COMPLETO.pdf Visibile a [TBR] Amministratori dell'archivio Download (96MB)
Anteprima	Testo BALZAMO_Chiara_36_PARZIALE.pdf Download (1MB) | Anteprima

Abstract

BACKGROUND: Human adult gastric stem cells (hAGSCs), due to their self-renewal capability and multipotency, play a significant role in stomach tissue regeneration and aging. However, hAGSC cellular homeostasis in gastric tissue physiopathology is poorly understood because the knowledge of their identity is still limited. GOAL: The purpose of this work was to explore the biological dynamics of Neck, Chief, and Isthmus stem cells within a physiological context. AIMS: To define the hAGSC cytotype-specific bio-markers, we performed bioinformatic data mining on open-access human gastric RNAseq single-cell databases and The Human Protein Atlas portal. Furthermore, to standardize a reliable source of hAGSCs to characterize their molecular features, we generated organoids with bio-marker promoter sequences upstream of the eGFP target gene. RESULTS: We identified AQP5, MUC6, and A4GNT for the isolation of Neck cells; PGC and 3 novel bio-markers (TMEM97, TMED6, and ELAPOR1) for the isolation of Chief cells; TK1 and EDEM3 as novel candidates for the isolation of Isthmus cells. We standardized an ex vivo organoid line that resembles the in vivo expression of these bio-markers. Finally, we isolated the PGC+ and A4GNT+ populations, making them accessible for further molecular characterization. In summary, we defined a methodology for the isolation of gastric epithelial cells and, for the first time, purified enriched populations of PGC and A4GNT positive cells using organoids. These results could help follow the hAGSC during homeostasis of the gastric mucosa.

Downloads

Actions (login required)

Modifica documento