Project description:Bone marrow (BM) is normally maintained in an immune-privileged and anti-inflammatory state, kept in check principally by regulatory T cells (Tregs). Thus, it is reasonable to expect that Tregs will help shield hematopoietic stem cells (HSCs) from excessive inflammation and thereby counteract HSC aging. Understanding how BM Tregs are adapted to the aged BM and whether they are endowed with unique functions to modulate HSC aging will identify targets for prevention of HSC aging. To identify the phenotype switching and function variation in BM Tregs with physiological and premature aging, we performed RNA-seq of Tregs from the bone marrow of mice at three months post irradiation (IR) and their age-matched control mice (Ctrl).
Project description:Recent advances have taken advantage of various animal models in HSC aging research, including certain gene mutations, chemicals, and ionizing radiation (IR). To identify the underlying mechanisms and phenotype switching in HSC aging, we employed IR-induced premature HSC aging model and performed RNA-seq of HSCs from the bone marrow (BM) of mice at three months post IR and their age-matched control mice (Ctrl).
Project description:Diminishing potential to replace damaged tissues is a hallmark for aging of somatic stem cells, but the mechanisms leading to aging remain elusive. We performed a proteome-wide analysis of human hematopoietic stem and progenitor cells (CD34+) along with five other cell types that constitute the bone marrow niche, namely, lymphocytes and precursors; monocytes/macrophages and precursors; granulocytic precursors and erythroid precursors, as well as mesenchymal stem/stromal cells. In total, we analyzed 270 samples from 59 human subjects. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models.
Project description:Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells (MSCs), the true identity of MSCs and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined MSCs and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a new component of marrow adipose tissue.
Project description:Hematopoietic stem cells give rise to all blood lineages, can fully re-populate the bone marrow, and easily outlive the host organism. To better understand how stem cells remain fit during aging, we analyzed the proteome of hematopoietic stem and progenitor cells.