Cell-cell interactome of the hematopoietic niche and its changes in acute myeloid leukemia

Sarah Ennis; Alessandra Conforte; Eimear O'Reilly; Javid Sabour Takanlu; Tatiana Cichocka; Sukhraj Pal Dhami; Pamela Nicholson; Philippe Krebs; Pilib Ó Broin; Eva Szegezdi

doi:10.1016/j.isci.2023.106943

Cell-cell interactome of the hematopoietic niche and its changes in acute myeloid leukemia

iScience. 2023 May 23;26(6):106943. doi: 10.1016/j.isci.2023.106943. eCollection 2023 Jun 16.

Authors

Sarah Ennis^{1

2}, Alessandra Conforte³, Eimear O'Reilly³, Javid Sabour Takanlu³, Tatiana Cichocka³, Sukhraj Pal Dhami³, Pamela Nicholson⁴, Philippe Krebs⁵, Pilib Ó Broin^{1

2}, Eva Szegezdi^{1

3}

Affiliations

¹ The SFI Centre for Research Training in Genomics Data Science, Galway, Ireland.
² Discipline of Bioinformatics, School of Mathematical & Statistical Sciences, University of Galway, H91 TK33 Galway, Ireland.
³ Apoptosis Research Centre, School of Biological & Chemical Sciences, University of Galway, H91 TK33 Galway, Ireland.
⁴ Next Generation Sequencing Platform, University of Bern, Bern, Switzerland.
⁵ Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland.

Abstract

The bone marrow (BM) is a complex microenvironment, coordinating the production of billions of blood cells every day. Despite its essential role and its relevance to hematopoietic diseases, this environment remains poorly characterized. Here we present a high-resolution characterization of the niche in health and acute myeloid leukemia (AML) by establishing a single-cell gene expression database of 339,381 BM cells. We found significant changes in cell type proportions and gene expression in AML, indicating that the entire niche is disrupted. We then predicted interactions between hematopoietic stem and progenitor cells (HSPCs) and other BM cell types, revealing a remarkable expansion of predicted interactions in AML that promote HSPC-cell adhesion, immunosuppression, and cytokine signaling. In particular, predicted interactions involving transforming growth factor β1 (TGFB1) become widespread, and we show that this can drive AML cell quiescence in vitro. Our results highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment, fostering AML growth.

Keywords: Cell biology; Hematology; Molecular biology.