Related Experiment Video
Updated: Jun 18, 2025
11:00
Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
7.2K
HES1 is required for mouse fetal hematopoiesis
Anthony Z Zhu1,2, Zhilin Ma3, Emily V Wolff1,2
1Division of Hematology and Oncology, University of Pittsburgh School of Medicine, 5117 Center Ave, Pittsburgh, PA, 15213, USA.
Stem Cell Research & Therapy
|July 29, 2024
Summary
Hairy and enhancer of split 1 (HES1) is crucial for fetal blood stem cell development. Loss of HES1 impairs fetal hematopoiesis by affecting cell proliferation and survival, with potential therapeutic targets identified.
Area of Science:
- Hematopoiesis research
- Stem cell biology
- Developmental biology
Background:
- Mammalian hematopoiesis involves hematopoietic stem cells (HSCs) generating all blood cell types.
- Hairy and enhancer of split (HES) repressors are known regulators of adult HSC development via Notch signaling.
Purpose of the Study:
- Investigate the role of HES1 in fetal hematopoiesis.
- Utilize a conditional knockout mouse model for embryonic hematopoietic specific Hes1 deletion.
Main Methods:
- Phenotypic flow cytometry
- Histopathology analysis
- In vitro colony forming unit (CFU) assay
- In vivo bone marrow transplant (BMT) assay
Main Results:
- Loss of Hes1 in early embryos caused smaller size, reduced hematopoietic stem progenitor cell (HSPC) pool, and defective multi-lineage differentiation.
- Hes1-deficient fetal hematopoietic cells showed decreased in vitro progenitor activity and compromised in vivo repopulation.
- Defects stemmed from reduced proliferation and increased apoptosis, linked to de-repressed HES1 targets p27 and PTEN.
- Inhibiting p27 or PTEN improved fetal HSPC function.
Conclusions:
- HES1 plays a significant, previously unrecognized role in regulating fetal hematopoiesis.
- Findings offer new insights into the distinct mechanisms of fetal versus adult HSC maintenance.
Related Concept Videos
01:21Hematopoiesis
5.2K
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...
5.2K
01:20Overview of Hematopoiesis
3.9K
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...
3.9K
01:19Multipotency of Hematopoietic Stem Cells
3.0K
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...
3.0K
01:01Regulation of Hematopoietic Stem Cells
3.2K
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...
3.2K
01:34Production of Formed Elements
1.4K
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...
Most HSCs commit to...
1.4K
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K