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Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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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...
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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
3.0K
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

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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...
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Hematopoiesis01:21

Hematopoiesis

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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
Production of Formed Elements01:34

Production 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...
1.4K
Overview of Hematopoiesis01:20

Overview 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...
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Related Experiment Video

Updated: Jun 25, 2025

Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells
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Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells

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BRD9 regulates normal human hematopoietic stem cell function and lineage differentiation.

Swati Garg1,2, Wei Ni1,2, Basudev Chowdhury1,2

  • 1Dana-Farber Cancer Institute, Dept. of Medical Oncology, Boston, MA, 02215, USA.

Cell Death and Differentiation
|May 30, 2024
PubMed
Summary
This summary is machine-generated.

Bromodomain-containing protein 9 (BRD9) is crucial for normal human blood cell development. Inhibiting BRD9 impairs hematopoietic stem cell function and differentiation, highlighting its role in epigenetic regulation.

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Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
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Area of Science:

  • Hematology
  • Epigenetics
  • Chromatin Biology

Background:

  • Bromodomain-containing protein 9 (BRD9) is part of the non-canonical BRG1/BRM-associated factor (ncBAF) chromatin remodeling complex.
  • BRD9 is a known synthetic lethal target in acute myeloid leukemia (AML).
  • The function of BRD9 in normal human hematopoiesis remains largely unknown.

Purpose of the Study:

  • To investigate the role of BRD9 in normal human hematopoietic stem and progenitor cell (HSPC) function.
  • To elucidate the molecular mechanisms by which BRD9 influences hematopoiesis.

Main Methods:

  • Genomic and chemical inhibition of BRD9 in human HSPCs.
  • In vitro colony-forming assays (GEMM colonies).
  • Lineage-specific differentiation cultures.
  • Xenotransplantation assays.
  • RNA sequencing (RNAseq) and chromatin accessibility analysis.
  • GATA1-luciferase reporter assays.

Main Results:

  • BRD9 inhibition in HSPCs resulted in reduced proliferation and stem cell loss.
  • Reduced BRD9 levels impaired the formation of immature mixed multipotent GEMM colonies.
  • BRD9 knockdown led to megakaryocytic differentiation failure, delayed erythroid differentiation, and enhanced myeloid differentiation.
  • HSPCs with BRD9 knockdown showed reduced long-term multilineage engraftment in vivo.
  • RNAseq revealed downregulated genes and increased chromatin accessibility at repressive transcription factor promoters upon BRD9 knockdown.
  • BRD9 loss modulated gene networks regulated by the hematopoietic master regulator GATA1, with BRD9 inhibition reducing GATA1 activity.

Conclusions:

  • BRD9 plays a critical role in maintaining active transcription during human HSC differentiation.
  • BRD9 is essential for proper hematopoietic stem cell function and multilineage differentiation.
  • BRD9 influences hematopoiesis through epigenetic regulation, impacting key transcription factors like GATA1.