Project 1 - Functional heterogeneity of human stromal cells: from basic science to clinical applications

Research Topic

Séverine Loisel, PhD (engineer); Tony Marchand, MD PhD (hospital practitioner); Nicolas Bertheuil, MD PhD (hospital practitioner);  Florence Jouan (engineer); Frédéric Mourcin, PhD (CR EFS); David Roulois, PhD (CRCN Inserm)

Recent scRNA-seq studies have identified various specialized stromal cell subsets defining specific spatial and functional niches that control the differentiation of hematopoietic cells or the development of adaptive immune responses within bone marrow (BM) and lymph nodes (LN). However, despite recent advances in the characterization of lymphoid stromal cell (LSC) and BM stromal cell origin, heterogeneity, and function in mice, little is known in human.

We recently revealed that both native and clinical-grade human mesenchymal stromal cells (MSC) obtained from BM and adipose tissue exhibit tissue-specific gene expression profile with direct functional consequences on their immune-regulatory properties (Ménard, Stem Cells 2020). Moreover, our work on follicular lymphoma LSC phenotypic and functional features further sustains a higher level of human stromal cell plasticity than previously anticipated from ex vivo expanded cells.

Specific aims adressed in our project

This project aims at deciphering the functional heterogeneity of human native stromal cells from LN, BM, and adipose tissue and how it impacts their clinical use. To do so, we use state-of-the-art techniques of transcriptomic and phenotypic analyses backed up with functional assays and mouse models to address:

  • Heterogeneity and origin of stromal cell precursors and lymphoid stromal cells
  • Heterogeneity and clinical applications of human stromal cells