Related Experiment Video
Updated: Jul 16, 2026
11:40
Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
Published on: October 20, 2014
Ott1(Rbm15) has pleiotropic roles in hematopoietic development
Glen D Raffel1, Thomas Mercher, Hirokazu Shigematsu
1Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. graffel@bidmc.harvard.edu
Summary
OTT1(RBM15) is crucial for B cell development and normally suppresses myeloid and megakaryocyte expansion. Its absence in mice disrupts hematopoietic stem cell differentiation, impacting multiple blood cell lineages.
Area of Science:
- Hematopoiesis
- Molecular Biology
- Cancer Pathogenesis
Background:
- OTT1 (RBM15) was identified as a translocation partner in infant acute megakaryocytic leukemia.
- OTT1 shares homology with the spen/Mint/SHARP family, possessing RNA recognition motifs and a transcriptional repressor domain.
- The physiological function of OTT1 in normal hematopoiesis remained undefined.
Purpose of the Study:
- To define the role of OTT1 in hematopoiesis.
- To elucidate the mechanism of t(1;22) acute megakaryocytic leukemia pathogenesis.
Main Methods:
- Generation of a conditional allele of Ott1 in mice.
- Deletion of Ott1 in adult mice to assess its function.
- Analysis of hematopoietic cell populations in spleen and bone marrow.
Main Results:
- Ott1 deletion in adult mice led to a loss of peripheral B cells due to blocked pro/pre-B differentiation.
- Observed myeloid and megakaryocytic expansion in spleen and bone marrow.
- Increased hematopoietic stem cells (Lin(-)Sca-1(+)c-Kit(+)) and a shift towards granulocyte differentiation.
Conclusions:
- Ott1 is required for B lymphopoiesis.
- Ott1 plays inhibitory roles in myeloid, megakaryocytic, and progenitor cell compartments.
- Dysregulation of OTT1 may contribute to OTT1-MAL-mediated leukemogenesis, particularly affecting the megakaryocyte lineage.
Related Concept Videos
01:28Role of Hematopoietic Growth Factors
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
01:21Lineage Commitment
Commitment is the process whereby stem cells:
01:19Multipotency of Hematopoietic Stem Cells
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
01:01Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
01:21Hematopoiesis
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
01:20Overview of Hematopoiesis
Hematopoiesis, or blood cell production, is a vital biological process that begins early in embryonic development and continues throughout life. This process generates the various types of cells found in blood, including red blood cells, white blood cells, and platelets from hematopoietic stem cells (HSCs).
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...