We have previously characterized stromal progenitor cells contained in fetal bone marrow by fluorescence-activated cell sorting (FACS) using the differential expression of CD34, CD38, and HLA-DR, and found that a small number were contained within the CD34(+) cell fraction. In the present study, the frequency of stromal progenitors in both the CD34+ and CD34- subpopulations from samples of feta...

At different developmental stages, candidate human hematopoietic stem cells (HSCs) are present within the CD34+ CD38- population. By means of xenotransplantation, such CD34+CD38- cells were recently shown to engraft the hematopoietic system of fetal sheep and nonobese diabetic severe combined immunodeficient adult mice. Here it is demonstrated that, after their injection into murine blastocysts...

One unique feature of vertebrate definitive hematopoiesis is the ontogenic switching of hematopoietic stem cells from one anatomical compartment or niche to another. In mice, hematopoietic stem cells are believed to originate in the aorta-gonad-mesonephros (AGM), subsequently migrate to the fetal liver (FL) and finally colonize the bone marrow (BM). Yet, the differentiation potential of hematop...

Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem progenitor cells obtained from healthy donors, CRISPR-Cas9 targeting the erythroid-...

OBJECTIVE in midtrimester fetuses the principal site of hematopoiesis is the liver. In hematopoietic organs, stromal cells such as fibroblasts, epithelial cells, and macrophage-like cells develop networks to maintain hematopoiesis, i.e. hematopoietic stem cell self-renewal, proliferation, and growth, by interaction with hematopoietic progenitor cells. ECM glycoproteins produced by the stromal c...

For many years it has been assumed that the ontogeny of the mammalian hematopoietic system involves sequential transfers of hematopoietic stem cells (HSCs) generated in the yolk sac blood islands, to successive hematopoietic organs as these become active in the embryo (fetal liver, thymus, spleen and eventually bone marrow). Very little was known about early events related to hematopoiesis that...

Murine embryonic stem (ES) cells are permanent blastocyst-derived cell lines capable of contributing to a wide variety of tissues, including the germ line, after injection into host blastocysts. Recently, we have shown that ES cells can produce all of the cells of the developing fetus after aggregation with developmentally compromised tetraploid embryos. Completely ES cell-derived embryos die p...

objective: nowadays, cord blood hematopoietic stem cells (hscs) are known as a valuable source for bone marrow transplantation but unfortunately their insufficient number is a limiting factor for using them in adult bone marrow transplantation. cord blood hcss expansion is an approach to overcome this problem, by inducing their self-renewal. tgf-b signaling pathway is a key inhibitory agent for...

Hematopoietic stem cells (HSCs) originate within the aortic-gonado-mesonephros (AGM) region of the midgestation embryo, but the cell type responsible for their emergence is unknown since critical hematopoietic factors are expressed in both the AGM endothelium and its underlying mesenchyme. Here we employ a temporally restricted genetic tracing strategy to selectively label the endothelium, and ...

chronic myeloid leukemia (cml) is a myeloproliferative disease of the hematopoietic stem cells, characterized by the presence of the philadelphia (ph) chromosome. although imatinib inhibits the bcr-abl kinase activity, clinical experiences confirm that imatinib may not target cml stem cells in vivo. the identification of signaling pathways responsible for the self-renewal properties of leukemic...