Bone Marrow Structure and Hematopoiesis

Bone marrow is the soft tissue filling the cavities of bones and the principal site of blood cell formation after birth. Within a meshwork of stromal cells, sinusoidal vessels, and extracellular matrix, hematopoietic stem cells give rise to all the erythroid, myeloid, and lymphoid lineages of blood through the process of hematopoiesis.

Definition

Bone marrow is the hematopoietic and stromal tissue within bone cavities in which hematopoietic stem cells, supported by a specialized niche, proliferate and differentiate into the cellular elements of blood.

Scope

This topic covers the histological organization of the bone marrow, the concept of the hematopoietic stem cell and its niche, and the broad pathway of blood cell production. It is a structural and cell-biological overview; it does not cover the diagnosis or treatment of marrow disorders or transplantation practice.

Core questions

• How is the bone marrow organized histologically?
• What is a hematopoietic stem cell and how is it defined?
• How does the marrow microenvironment (niche) regulate stem cells?
• How do blood lineages arise from a common precursor?

Key concepts

• Hematopoietic stem cell self-renewal and multipotency
• The stromal/vascular niche
• Stem-cell quiescence and activation
• Sinusoidal vasculature and cell release into blood
• Myeloid and lymphoid differentiation hierarchy
• Red (active) versus yellow (fatty) marrow

Mechanisms

Bone marrow houses hematopoietic stem cells within a niche of stromal cells, blood vessels, and matrix that controls whether they remain quiescent or proliferate. These stem cells self-renew and give rise to progressively committed progenitors of the erythroid, myeloid, and lymphoid lineages, an evolving hierarchy reviewed by Orkin and Zon. Single human cells with long-term multilineage engraftment have been prospectively isolated, confirming the stem cell as a discrete entity, and lineage-tracing work shows that most stem cells are deeply quiescent yet can reversibly switch to active division during stress. Mature cells exit through the thin-walled marrow sinusoids into the circulation.

Clinical relevance

Bone marrow architecture and the stem-cell concept underlie the interpretation of the marrow aspirate and biopsy and the rationale for hematopoietic transplantation. As a reference topic this describes normal marrow structure and the biology of blood cell formation; it is not a basis for individual diagnosis or treatment.

History

The idea that a single multipotent cell sustains all blood lineages grew from mid-twentieth-century transplantation and colony-forming experiments and matured into the modern hematopoietic stem-cell concept. Prospective isolation of single human stem cells with durable multilineage output and the demonstration of reversible stem-cell dormancy refined this picture, while the recognition of a regulatory marrow niche reframed hematopoiesis as a property of cells in their microenvironment.

Debates

How hierarchical is hematopoiesis?

The classical stepwise tree from a single stem cell through fixed intermediate progenitors has been questioned by single-cell studies suggesting more continuous and heterogeneous differentiation, and the exact structure of the hierarchy remains under discussion.

Key figures

• Stuart Orkin
• Sean Morrison
• David Scadden
• John Dick
• Andreas Trumpp

Seminal works

• orkin-zon-2008
• notta-2011
• morrison-scadden-2014

Frequently asked questions

What is a hematopoietic stem cell?

It is a rare bone marrow cell that can both renew itself and give rise to all the lineages of blood; single such human cells have been isolated and shown to reconstitute long-term, multilineage blood formation.

What is the bone marrow niche?

The niche is the local microenvironment of stromal cells, blood vessels, and signals that surrounds hematopoietic stem cells and regulates whether they stay quiescent or divide.