The bone marrow stroma in human myelodysplastic syndrome reveals alterations that regulate disease progression.

Myelodysplastic syndromes (MDSs) are a heterogenous group of diseases affecting the hematopoietic stem cell that are curable only by stem cell transplantation. Both hematopoietic cell intrinsic changes and extrinsic signals from the bone marrow (BM) niche seem to ultimately lead to MDS. Animal models of MDS indicate that alterations in specific mesenchymal progenitor subsets in the BM microenvironment can induce or select for abnormal hematopoietic cells.

tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche.

Extracellular vesicles (EVs) transfer complex biologic material between cells. However, the role of this process in vivo is poorly defined. Here, we demonstrate that osteoblastic cells in the bone marrow (BM) niche elaborate extracellular vesicles that are taken up by hematopoietic progenitor cells in vivo.

A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia.

Stroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis, and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA sequencing (scRNA-seq) to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy.

Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells.

The mTOR pathway is a critical determinant of cell persistence and growth wherein mTOR complex 1 (mTORC1) mediates a balance between growth factor stimuli and nutrient availability. Amino acids or glucose facilitates mTORC1 activation by inducing RagA GTPase recruitment of mTORC1 to the lysosomal outer surface, enabling activation of mTOR by the Ras homolog Rheb. Thereby, RagA alters mTORC1-driven growth in times of nutrient abundance or scarcity.

Shipping mouse bone marrow: Keep it in the bone.

Sharing reagents is of self-evident value in life science research, however, primary cell populations often do not cryopreserve well or can require extensive preparation by collaborators, making shipping difficult. Here we report an evaluation of different conditions for the storage shipment of mouse bone marrow (BM) cells that would best preserve the number, viability, and frequency of different hematopoietic lineages, as well as functionality of progenitor populations. Bones were either crushed to release BM cells or stored intact in one of three media: Phosphate buffered saline (PBS) supplemented with 2% fetal bovine serum (FBS), Plasmalyte, or RPMI at 4°C.

Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.

Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location.