Cell-cell Interactome of the Hematopoietic Niche and Its Changes in Acute Myeloid Leukemia

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jun 19

PMID 37332612

Authors

Sarah Ennis

Alessandra Conforte

Eimear OReilly

Javid Sabour Takanlu

Tatiana Cichocka

Sukhraj Pal Dhami

Pamela Nicholson

Philippe Krebs

Pilib O Broin

Eva Szegezdi

Affiliations

Soon will be listed here.

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 . Our results highlight potential mechanisms of enhanced AML-HSPC competitiveness and a skewed microenvironment, fostering AML growth.

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