The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia

Frimberger, Angela E.; McAuliffe, Christina; Werme, Kimberly; Tuft, Richard A.; Fogarty, Kevin E.; Benoit, Brian O.; Dooner, Mark S.; Quesenberry, Peter J.

doi:10.1046/j.1365-2141.2001.02542.x

Cited by 51 publications

(48 citation statements)

References 29 publications

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“…The finding of rapid in vitro homing is concordant with the results of other in vitro adhesion studies 27 as well as with our own finding that 82% Ϯ 7% of lineage-negative, rhodamine-dull, Hoechst-dull (lin Ϫ rho low Ho low ) cells adhered to individual stromal cells within 1 hour of contact. 52 Further, other studies have shown that in vivo homing plateaus within the first few hours after transplantation 16,19 also agreeing with the results we present here.…”

Section: Discussionsupporting

confidence: 83%

An in vitro model of hematopoietic stem cell homing demonstrates rapid homing and maintenance of engraftable stem cells

Frimberger

Stering

Quesenberry

2001

Blood

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Hematopoietic stem cell (HSC) homing is believed to rely heavily on adhesion interactions between stem cells and stroma. An in vitro assay was developed for adhesion of engraftable HSCs in bone marrow suspensions to pre-established Dextertype long-term bone marrow culture stromal layers. The cell numbers in the adherent layer and supernatant were examined, along with the engraftment capability of adherent layer cells to indicate the number of HSCs that homed to in vitro stroma. The cell number in the supernatant declined over the 24-hour period. The number of test cells adhering to the stromal layer increased during the first hour and then fell at 6 and 24 hours. The number of test HSCs adhering to the stromal layer was substantial at 20 minutes, increased during the first hour, and then remained constant at 1, 6, and 24 hours of adhesion. These data indicate that adhesion of engraftable HSCs occurs quickly and increases during the first hour of contact with pre-established stroma, that adhesion plateaus within 1 hour of contact, and that HSCs maintain their engraftment capability for at least 24 hours of stromal adhesion. Long-term engraftment from test cells at more than 1 hour of adhesion represents 70.7% of the predicted engraftment from equivalent numbers of unmanipulated marrow cells, indicating that 2 of 3 test engraftable HSCs adhered. These findings demonstrate the usefulness of this model system for studying stemstromal adhesion, allowing further dissection of the mechanism of HSC homing and exploration of possible manipulations of the process. IntroductionHematopoietic stem cell (HSC) homing is the process by which HSCs, infused intravenously in the transplantation setting, specifically extravasate in the bone marrow to engraft and proliferate there. Homing has been studied extensively both in vivo and in vitro and is believed to rely on adhesion molecule interactions between stromata, which consist of stromal cells and extracellular matrix, and stem cells. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] In vivo homing studies typically rely on infusion of a labeled or detectable HSC population and subsequent detection at various times after the transplantation. 16,19 In this approach, the recipients must be examined early enough (approximately 24 hours or earlier) that only infused cells, and not their progeny, are detected. However, testing this early can make it difficult to ascertain that the cells are truly homed and not migratory. Also, to dissect the mechanisms of homing, it would be desirable to conduct various manipulations, such as adding an adhesion receptor blocking antibody, and this can be cumbersome or even impossible in vivo. On the other hand, in vitro systems are relatively easy to manipulate, but the assay result can be difficult to interpret. Most in vitro homing studies examine adhesion of a hematopoietic cell population or cell line to a test substrate, such as purified extracellular matrix molecule coatings or stromal cell lines, under various conditions. 20-29 ...

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Section: Discussionsupporting

confidence: 83%

An in vitro model of hematopoietic stem cell homing demonstrates rapid homing and maintenance of engraftable stem cells

Frimberger

Stering

Quesenberry

2001

Blood

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“…They are highly motile, showing very rapid directed movement and rapid membrane deformation on cytokine exposure. 44 These cells also express a large number of stem cell-specific genes. Phillips et al 45 have reported on 2119 nonredundant gene products from fetal liver hematopoietic stem cells, using a subtracted cDNA library to generate a micro array chip.…”

Section: Stem Cell Genes and Functionsmentioning

confidence: 99%

The chiaroscuro stem cell: a unified stem cell theory

Quesenberry

Colvin

Lambert

2002

Blood

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Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell popula- IntroductionWe present here a different view of early hematopoiesis. This is not the standard dogma of many investigators in the field, but is built upon solid work by many laboratories over many years. This is a perspective, and thus naturally reflects the biases of the authors. These, in turn, have a basis in many published studies from our laboratory and other laboratories and also from extensive unpublished, but abstracted, data from our laboratory. It is appropriate to consider this contribution as speculative in nature.The term chiaroscuro refers to the treatment of light and shade in painting. Our current view of the changing phenotype of the marrow stem cell suggests a chiaroscuro nature to this picture.In general, models of stem cell regulation have been hierarchical. 1,2 A primitive stem cell, with great potential, gives rise to a proliferating progenitor pool, which in turn gives rise to recognizable differentiated cells. During this process, proliferative potential is lost, while specific differentiated features are acquired. Presumptively, but without definite proof, there is also self-renewal at the most primitive stem cell level, and this is also lost with differentiation. Many data exist to support such a hierarchical model. Marrow cells have been separated with short-and long-term repopulation potential 3,4 and progenitors have been characterized as exclusively committed to the production of restricted progeny. 5,6 In addition, the clear expansion of different progenitor types in cytokinestimulated in vitro culture with a loss of long-term engraftment capacity speaks to the existence of a progenitor hierarchy, at least at the more differentiated progenitor levels. 7,8 A model encompassing these features is shown in Figure 1.This model does not fit with all published data. For instance, the "daughter cell" or paired-progenitor experiments of Suda and colleagues 9 indicate that a primitive progenitor cell can make totally different lineage choices during one cell cycle transit, such that, for example, one daughter cell forms an erythroid colony while the other daughter (or sister) cell forms a neutrophilmacrophage colony. Out of a total of 387 pairs evaluated, 68 pairs of colonies consisted of dissimilar com...

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“…Two different morphologies of pseudopodia have been reported (7). Magnupod extensions, described as thin, occurring at large distances (>300 μm) from the main cell body and showing rapid dynamic behavior, have been proposed by several groups to be equivalent to the structures known as cytonemes (29) or proteopodia (4,30). However, tenupodia correspond to those previously described as 'retraction fibers' (30,31).…”

Section: Discussionmentioning

confidence: 97%

“…A variety of actin-based cell surface membrane projections has been described in hematopoietic cells, including microvilli, lamellipodia, microspikes and filopodia (4). The Rho family of GTPases and the WASP family have been shown to be involved in the signal-transduction pathways that induce the formation of these projections.…”

Section: Introductionmentioning

confidence: 99%

Novel membrane cell projection defects in Wiskott-Aldrich syndrome B cells

Andreu

Aran²,

Fillat³

2007

Int J Mol Med

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Abstract. Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, autoimmune disorders and an increased incidence of malignancies. This complex phenotype results from mutations in the WASP gene. WASP is a key member of a protein family that links signaling pathways to actin cytoskeleton reorganization by activating Arp2/3-mediated actin polymerization. Actin polymerization defects have been extensively defined in WAS T cells and also in dendritic cells and macrophages, but few reports have concentrated on WAS B cells. In the present study, we investigated cytoskeleton abnormalities in WAS B cell lines. For the first time we report alterations in the capacity of these cells to extend filopodia in response to bradykinin stimuli and an impairment in the formation of long pseudopodia under basal conditions. Such alterations most probably result from a WASP dysfunction, given that a retroviral gene transfer of a corrected form of the WASP gene was able to rescue the abnormal phenotypes.

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The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia

Cited by 51 publications

References 29 publications

An in vitro model of hematopoietic stem cell homing demonstrates rapid homing and maintenance of engraftable stem cells

An in vitro model of hematopoietic stem cell homing demonstrates rapid homing and maintenance of engraftable stem cells

The chiaroscuro stem cell: a unified stem cell theory

Novel membrane cell projection defects in Wiskott-Aldrich syndrome B cells

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