| Summary: | The development of mouse genetic tools has made a significant contribution to the understanding of skeletal and hematopoietic stem cell niches in bone marrow (BM). However, many experimental designs (e.g., selections of marker genes, target vector constructions, and choices of reporter murine strains) have unavoidable technological limitations and bias, which lead to experimental discrepancies, data reproducibility issues, and frequent data misinterpretation. Consequently, there are a number of conflicting views relating to fundamental biological questions, including origins and locations of skeletal and hematopoietic stem cells in the BM. In this report, we systematically unravel complicated data interpretations via comprehensive analyses of technological benefits, pitfalls, and challenges in frequently used mouse models and discuss their translational relevance to human stem cell biology. Particularly, we emphasize the important roles of using large human genomic data-informatics in facilitating genetic analyses of mouse models and resolving existing controversies in mouse and human BM stem cell biology. : In this article, Chen and colleagues discuss technological challenges for genetic analysis of bone marrow stem cell niches. This article consists of a concise review, considerable perspectives, and in-depth data analysis. Importantly, the authors provide translational relevance through interrogating mouse genetic models with human genomic datasets. This review would aid to resolve data inconsistencies and their associated stem cell controversies. Keywords: stem cell niches, cell identity, bone marrow stromal cells, skeletal stem cells, hematopoietic stem cells, mouse genetics, genomics, epigenomics, nestin, leptin receptor
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