Two different levels of control for bone marrow hematopoiesis are believed to exist. On the one hand, normal blood cell distribution is believed to be maintained in healthy subjects by an "innate" hematopoietic activity, i.e., a basal intrinsic bone marrow activity. On the other hand, an "adaptive" hematopoietic state develops in response to stress-induced stimulation. This adaptive hematopoies...

Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitinati...

Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakary...

Hematopoiesis is defined as the formation of all types of blood cells from hematopoietic stem cells (HSCs) (Orkin and Zon, 2008). This complex process involves the coordination of intrinsic master blood transcriptional regulators and signaling molecules from the surrounding tissues (Huang and Zon, 2008). Understanding the molecular and cellular mechanisms that drive normal hematopoiesis and hem...

Recent genetic analyses of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human aging. Clonally restricted hematopoiesis is associated with an increased risk of subsequent diagnosis of myeloid or lymphoid neoplasia and increased all-cause mortality. Although myelodysplastic syndromes (MDS) are defined by cyt...

The bone marrow (BM) microenvironment or the hematopoietic stem cell (HSC) niche is normally hypoxic, which maintains HSC quiescence. Paradoxically, transplanted HSCs rapidly proliferate in this niche. Pretransplant myelosuppression results in a substantial rise in oxygen levels in the marrow microenvironment due to reduced cellularity and consequent low oxygen consumption. Therefore, it may be...

We previously reported a transgenic mouse model expressing herpesvirus thymidine kinase (TK) gene under the control of a 2.3-kilobase fragment of the rat collagen 1 type I promoter (Col2.3 TK). This construct confers lineage-specific expression in developing osteoblasts, allowing the conditional ablation of osteoblast lineage after treatment with ganciclovir (GCV). After GCV treatment these mic...

The following conclusions were drawn from the ferrokinetic studies using 59Fe in mice, whose hematological disorders were induced by various treatments. 1. The ferrokinetics in the normal mice were studied. 2. Chloramphenicol (CP) administration in mice first induced ferrokinetics disturbances and then suppressed erythropoiesis. 3. Splenectomy induced hypererythropoiesis in the bone marrow, and...

Embryonic liver is a transient site for definitive hematopoiesis. Along with maturation of the bone marrow and spleen, hematopoietic cells relocate from the liver to their final destinations while the liver starts organizing its own structure and develops numerous metabolic functions toward adult. Recently, it was demonstrated that the signal exerted by oncostatin M (OSM) through gp130 plays a ...

Interleukin (IL)-12 synergizes with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors in vitro. However, in vivo administration of IL-12 decreases peripheral blood counts and bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor-deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of hematopoiesis by...