Prospective isolation of nonhematopoietic cells of the niche and their differential molecular interactions with HSCs

Abstract

The bone marrow niche environment is essential for the control and maintenance of hematopoietic stem cells (HSCs). The investigators present the first global analysis of the communication between distinct niche cell types and HSCs.

Hyperleukocytosis and Leukostasis in Acute Myeloid Leukemia: Can a Better Understanding of the Underlying Molecular Pathophysiology Lead to Novel Treatments?

“…A major limitation to studying the HSC niche is the inability to maintain and expand murine HSC cultures over extended periods of time [ 29 ]. Furthermore, there have been discrepant results reported for the use of various Cre-targeted cell lines [ 24 ].…”

“…Furthermore, there have been discrepant results reported for the use of various Cre-targeted cell lines [ 24 ]. Recently, Mende et al published a computational method to study ligand-receptor interactions between HSCs and other niche cells on a messenger RNA expression level [ 29 ]. Using this technique the authors were able to show distinct receptor-ligand interactions between the various cells constituting the bone marrow niche with distinct effects on HSC function that could be altered by the addition of CXCL12 or E-selectin [ 29 ].…”

“…Recently, Mende et al published a computational method to study ligand-receptor interactions between HSCs and other niche cells on a messenger RNA expression level [ 29 ]. Using this technique the authors were able to show distinct receptor-ligand interactions between the various cells constituting the bone marrow niche with distinct effects on HSC function that could be altered by the addition of CXCL12 or E-selectin [ 29 ]. With the expansion of this technique to single-cell proteomic analyses, an even more granular description of the interactions within the bone marrow niche could be achieved which might allow for the identification of novel therapeutic targets.…”

Hematopoietic stem cells self-renew symmetrically or gradually proceed to differentiation

“…Understanding the mechanisms that regulate stem cell maintenance and output requires methods to quantify their behavior in vivo, without disrupting stem cell interactions with their niches (Morrison and Spradling, 2008;Mende et al, 2019). Cell-cycle-dependent labeling studies reported that HSCs divide infrequently (between 2 and 7% of HSCs per day) and indicate that they are not a uniform population in this respect (Kiel et al, 2007;Wilson et al, 2008;Foudi et al, 2009;Oguro et al, 2013;Akinduro et al, 2018).…”

Molecular interactome between HSCs and their niches

“…In this issue of Blood, Mende et al provide a computational method to infer potential ligand-receptor interactions between murine hematopoietic stem and progenitor cells (HSPCs) and their niche-forming cells. 1 Niches formed by mesenchymal stem cells (MSCs) associated with endothelial cells were suggested a decade ago as critical regulators of HSCs. 2,3 In the mouse, different genetic models have been used to mark MSCs, and it is agreed that these cells are an important source of key HSC factors.…”