Haematopoietic stem cells (HSCs) sustain multilineage haematopoiesis during the lifetime of an organism. Adult HSCs reside in dedicated bone marrow (BM) niches, which sustain their functions. Extensive efforts have been devoted into unveiling the HSC niche due to its medical relevance. [1][2][3][4][5][6] The BM constitutes a highly vascularised organ. Anatomically two major BM-niche regions can be distinguished: the vascular niche (including arterioles and sinusoids that converge in the central vein) and the endosteal niche, more closely associated with the bone 7 (Figure 1). Within the vascular niche, besides endothelial cells (ECs), which are an intrinsic part of the blood vessels, the stromal cells provide a tri-dimensional scaffold to the BM and include mesenchymal stem cells (MSCs), which are multipotent cells with the ability to differentiate into osteocytes, adipocytes and chondrocytes. MSCs comprise periarteriolar NG2 + cells, Nestin high cells, MYH11 + cells, CXCL12-abundant reticular (CAR) cells, perisinusoidal LepR + cells and Nestin low cells, amongst others. [1][2][3][4][5]7 In addition, sympathetic nerves and non-myelinating Schwann cells associate with arteries, while megakaryocytes (MKs) connect with sinusoids. In the endosteal niche, macrophages, osteoblasts and osteoclasts do not normally associate with the vasculature. 7 Interestingly, HSCs locate to specific areas within the BM. Particularly, HSCs concentrate close to the vasculature during homeostasis and closer to the endosteum after transplantation. 8 Different cell types have been

Summary Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato‐pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting evidence to suggest that BMAds are not just a simple structural entity of bone marrow microenvironments but a bona fide driver of physio‐ and pathophysiological processes relevant to multiple aspects of health and disease. Whilst the truly multifaceted nature of BMAds has only just begun to emerge, paradigms have shifted already for normal, malignant and non‐malignant haemopoiesis incorporating a view of adipocyte regulation. Major efforts are ongoing, to delineate the routes by which BMAds participate in health and disease with a final aim of achieving clinical tractability. This review summarises the emerging role of BMAds across the spectrum of normal and pathological haematological conditions with a particular focus on its impact on cancer therapy.

Colorectal cancer (CRC) is the third most frequent human cancer with over 1.3 million new cases globally. CRC is a complex disease caused by interactions between genetic and environmental factors; in particular, high consumption of red meat, including beef, is considered a risk factor for CRC initiation and progression. Recent data demonstrate that exogenous microRNAs (miRNAs) entering the body via ingestion could pose an effect on the consumer. In this study, we focused on bovine miRNAs that do not share a seed sequence with humans and mice. We identified bta‐miR‐154c, a bovine miRNA found in edible parts of beef and predicted via cross‐species bioinformatic analysis to affect cancer‐related pathways in human cells. When bovine tissue was subjected to cooking and a simulation of human digestion, bta‐miR‐154c was still detected after all procedures, albeit at reduced concentrations. However, lipofection of bta‐miR‐154c in three different colorectal human cell lines did not affect their viability as evaluated at various time points and concentrations. These data indicate that bta‐miR‐154c (a) may affect cancer‐related pathways in human cells, (b) can withstand digestion and be detected after all stages of an in vitro digestion protocol, but (c) it does not appear to alter epithelial cell viability after entering human enterocytes, even at supraphysiological amounts. Further experiments will elucidate whether bta‐miR‐154c exerts a different functional effect on the human gut epithelium, which may cause it to contribute to CRC progression through its consumption.