Beyond Stem Cells: Self-Renewal of Differentiated Macrophages

  title={Beyond Stem Cells: Self-Renewal of Differentiated Macrophages},
  author={Michael H Sieweke and Judith E. Allen},
Background Many mature cells of the body are continuously replaced, particularly in tissues that are most exposed to the environment such as cells of the immune system. The need for new cells is driven by cellular turnover during normal tissue homeostasis and is further increased upon infection. Because differentiated cells typically withdraw from the cell cycle, replacement of mature cells is generally thought to depend on differentiation of self-renewing, tissue-specific stem cells. Until… 

Establishment of bone marrow-derived M-CSF receptor-dependent self-renewing macrophages

The presence of adult bone marrow-derived macrophages that retain self-renewing capacity is shown and a new cell model is proposed that would be useful to unravel differences in phenotype, function, and molecular mechanism of proliferation among self-Renewing macrophage with different origins.

Tissue macrophage identity and self‐renewal

This review summarizes the current knowledge about the identity, proliferation, and turnover of tissue‐resident macrophages and how they differ from freshly recruited short‐lived monocyte‐derived cells and examines whether macrophage proliferation can be qualified as self‐renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self‐Renewal mechanisms in stem cells.

Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities

Although monocyte-derived F4/80hi macrophages eventually displace the embryonic population with age in a process that is highly gender dependent and not due to proliferative exhaustion of the incumbent embryonic population, despite the greater proliferative activity of newly recruited cells.

Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

It is shown that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells, like embryonic precursors if the niche is available to them.

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

Current understanding on the origin, ontogeny and fates of tissue macrophages are summarized and the molecular regulation of resident macrophage homeostasis in physiological situation is discussed.

Fetal liver endothelium regulates the seeding of tissue-resident macrophages

It is shown that an endothelium-specific molecule, plasmalemma vesicle-associated protein (PLVAP), regulates the seeding of fetal monocyte-derived macrophages to tissues in mice, and is the first molecule identified in any organ as regulating the migratory events during embryonic macrophage ontogeny.

Macrophages: development and tissue specialization.

Two major recent paradigm shifts in the understanding of tissue macrophage biology are reviewed, including the realization that most tissue-resident macrophages are established prenatally and maintained through adulthood by longevity and self-renewal and the recognition of tissue specialization in response to local environmental cues.

Functional significance of mononuclear phagocyte populations generated through adult hematopoiesis

Key features of monocyte differentiation are presented, focusing primarily on the developmental hierarchy that is established through this process, the markers used to identify discrete cell populations, and novel, functional attributes of these cells.

From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

This review will address some of the important questions under the general framework of the role of monocytes and macrophages in the initiation, development, resolution, and chronicization of inflammation.



A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells

It is found that the transcription factor Myb was required for development of HSCs and all CD11bhigh monocytes and macrophages, but was dispensable for yolk sac (YS)macrophages and for the development of YS-derived F4/80bright macrophage populations in several tissues.

Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network

Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end

Mechanisms of stem cell self-renewal.

In response to changing tissue demands, stem cells undergo changes in cell cycle status and developmental potential over time, requiring different self-renewal programs at different stages of life.

MafB/c-Maf Deficiency Enables Self-Renewal of Differentiated Functional Macrophages

It is reported that combined deficiency for the transcription factors MafB and c-Maf enables extended expansion of mature monocytes and macrophages in culture without loss of differentiated phenotype and function and thus appears possible to amplify functional differentiated cells without malignant transformation or stem cell intermediates.

A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation

Macrophage (MØ) biology is routinely modelled in the peritoneal cavity, a vascular tissue readily infiltrated by leukocytes during inflammation. After several decades of study, no consensus has

Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

It is shown that MDPs are in vivo precursors of BM and blood monocytes, and grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCS in the spleen, which develop during homeostasis from M DPs without a monocytic intermediate.

Langerhans cells arise from monocytes in vivo

It is established that CSF-1 receptor–deficient hematopoietic precursors failed to reconstitute the LC pool in inflamed skin and monocytes with high expression of the monocyte marker Gr-1 were specifically recruited to the inflamedskin, proliferated locally and differentiated into LCs.

Distinct bone marrow-derived and tissue resident macrophage-lineages proliferate at key stages during inflammation

It is shown that proliferation of both bone marrow-derived inflammatory and tissue resident macrophage lineage branches is a key feature of the inflammatory process with major implications for the mechanisms underlying recovery from inflammation.