Related Experiment Video
Updated: Jun 21, 2026
08:14
Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
Published on: December 3, 2015
Induction of granulocytic differentiation by 2 pathways
Pu Zhang1, Erik Nelson, Hanna S Radomska
1Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Blood
|May 31, 2002
Summary
CCAAT enhancer binding protein alpha (C/EBP alpha) is crucial for granulocyte development. Its deficiency causes myeloid blocks, but inducible C/EBP alpha expression or specific cytokines can restore granulocytic differentiation.
Area of Science:
- Hematology
- Molecular Biology
- Cellular Differentiation
Background:
- CCAAT enhancer binding protein alpha (C/EBP alpha) is essential for granulocytopoiesis.
- Deficiency in C/EBP alpha causes blocked myeloid development, observed in acute myelogenous leukemia.
- C/EBP alpha(-/-) fetal livers exhibit immature myeloid blasts lacking myeloid gene expression.
Purpose of the Study:
- To further characterize the block in granulocytic differentiation caused by C/EBP alpha deficiency.
- To investigate the role of C/EBP alpha in myeloid progenitor differentiation.
- To explore pathways regulating granulopoiesis.
Main Methods:
- Derived cell lines from C/EBP alpha-deficient fetal livers.
- Introduced an inducible C/EBP alpha gene into these cell lines.
- Stimulated C/EBP alpha(-/-) cells with cytokines (IL-3, GM-CSF) and all-trans retinoic acid.
Main Results:
- C/EBP alpha-deficient cell lines resembled immature myeloid blasts and lacked myeloid gene/marker expression.
- Conditional C/EBP alpha expression induced C/EBP beta, C/EBP epsilon, and granulocyte differentiation.
- Interleukin-3 and granulocyte-macrophage colony-stimulating factor also induced differentiation, unlike all-trans retinoic acid.
Conclusions:
- C/EBP alpha is a key regulator of granulopoiesis, controlling the expression of other C/EBP family members.
- At least two distinct pathways, involving C/EBP alpha induction or specific cytokines, can drive myeloid progenitor differentiation.
- Findings implicate C/EBP family members in the complex regulation of granulocyte development.
Related Concept Videos
01:21Lineage Commitment
Commitment is the process whereby stem cells:
01:15Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
01:31Antigen Processing Pathways
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
01:24B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...