Concise review: multiple niches for hematopoietic stem cell regulations.

Two types of stem cell niches in bone marrow (BM), endosteal osteoblastic, and vascular niches are involved in the microenvironmental regulation of hematopoietic stem cells (HSCs). Recently, redundant features of the two niches were identified, based on their common cellular origins or chemical mediators being produced in each niche. In contrast, studies have also revealed that HSCs are localized differentially in the niches with respect to their distinct functional status, and that the biological activity of each niche is differentially influenced by extrinsic conditions.

Disruption of bis leads to the deterioration of the vascular niche for hematopoietic stem cells.

The stem cell niche plays an important role in the microenvironmental regulation of hematopoietic stem cells, but the integration of niche activity remains poorly understood. In this study, we show that a functional deficiency of Bis/BAG-3/CAIR-1, a protein related to apoptosis and the response to cellular stress, results in perturbation of the vascular stem cell niche, causing a series of hematopoietic derangements. Mice with a targeted disruption of bis (bis(-/-)) exhibited a loss of hematopoietic stem cells and defective B-cell development.

Undifferentiated hematopoietic cells are characterized by a genome-wide undermethylation dip around the transcription start site and a hierarchical epigenetic plasticity.

Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is growing, but the genome-wide epigenetic signature of HSCs and its functional significance remain unclear. In this study, from a genome-wide comparison of CpG methylation in human CD34(+) and CD34(-) cells, we identified a characteristic undermethylation dip around the transcription start site of promoters and an overmethylation of flanking regions in undifferentiated CD34(+) cells. This "bivalent-like" CpG methylation pattern around the transcription start site was more prominent in genes not associated with CpG islands (CGI(-)) than CGI(+) genes.