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Hematopoiesis

Hematopoiesis

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...

Multipotency of Hematopoietic Stem Cells

Multipotency 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...

Overview of Hematopoiesis

Overview 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...

Production of Formed Elements

Production of Formed Elements

Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...

Regulation of Hematopoietic Stem Cells

Regulation 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...

Role of Hematopoietic Growth Factors

Role 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,...

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Combining Intravital Fluorescent Microscopy (IVFM) with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches

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An MLL-dependent network sustains hematopoiesis.

Erika L Artinger¹, Bibhu P Mishra, Kristin M Zaffuto

¹Department of Genetics , Institute for Quantitative Biomedical Sciences, and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

Proceedings of the National Academy of Sciences of the United States of America

|June 8, 2013

Summary

The histone methyltransferase Mixed Lineage Leukemia (MLL) regulates genes beyond Hox targets in hematopoietic stem cells. PR domain containing 16 partially rescues MLL-deficient cells, revealing MLL

Keywords:

HSC epigenetics proliferation

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Area of Science:

Molecular Biology
Hematopoiesis
Epigenetics

Background:

Mixed Lineage Leukemia (MLL) is crucial for hematopoietic stem cell maintenance and is implicated in leukemia.
While MLL's role in regulating Hox genes is known, its broader transcriptional network in normal hematopoiesis is uncharacterized.

Purpose of the Study:

To identify and characterize the MLL-dependent transcriptional network in hematopoietic stem cells.
To understand the distinctions between MLL's function in normal hematopoiesis and its role in leukemia.

Main Methods:

Utilized conditional loss-of-function models.
Performed genomewide expression analyses.
Conducted chromatin immunoprecipitation and functional rescue assays.

Main Results:

The MLL-dependent transcriptional network extends beyond previously known Hox targets.
Identified regulators of self-renewal within the MLL network, with both Menin-dependent and -independent targets.
PR domain containing 16 showed unique efficacy in rescuing MLL-deficient hematopoietic stem and progenitor cells.

Conclusions:

Highlights the tissue-specific regulatory roles of MLL/Trithorax family members.
Provides insights into MLL's distinct roles in normal hematopoiesis versus leukemia development.