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Related Concept Videos

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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Multipotency of Hematopoietic Stem Cells01:19

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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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Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

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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...
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Lymphoid Cells and Tissues01:18

Lymphoid Cells and Tissues

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Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Stem cell decoupling underlies impaired lymphoid development during aging.

Geunhyo Jang1, Stephania Contreras Castillo2, Eduardo Esteva1,3

  • 1Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2023
PubMed
Summary
This summary is machine-generated.

Aging impairs hematopoietic stem cells (HSCs) in mice, reducing their contribution to all blood cell types. This global decoupling, not myeloid bias, explains reduced lymphocyte production in older animals.

Keywords:
aginghematopoietic stem cellslymphopoiesis

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Area of Science:

  • Hematopoiesis research
  • Immunology
  • Gerontology

Background:

  • Mammalian aging causes hematopoietic stem cell (HSC) defects, notably impairing T and B lymphocyte development.
  • This defect is often attributed to an age-related accumulation of HSCs with myeloid bias.

Purpose of the Study:

  • To investigate the functional state of HSCs in aging mice.
  • To determine if myeloid bias or a global HSC defect underlies impaired lymphopoiesis.

Main Methods:

  • Inducible genetic labeling and lineage tracing of HSCs in unmanipulated old mice.
  • Single-cell RNA sequencing and CITE-Seq for HSC progeny analysis.
  • Competitive transplantation assays with genetically marked HSCs.

Main Results:

  • Old HSCs showed reduced differentiation potential across all lineages (lymphoid, myeloid, megakaryocytic).
  • HSC progeny in old mice maintained a balanced lineage spectrum, including lymphoid progenitors.
  • Lineage tracing confirmed reduced HSC contribution to all lineages.
  • Competitive transplantation showed old HSCs were compensated in myeloid lineages but not lymphoid lineages.

Conclusions:

  • Aging decouples HSCs from overall hematopoiesis, affecting all cell types.
  • This global decoupling, rather than myeloid bias, is the primary driver of impaired lymphopoiesis in aging mice.