3D collagen matrices modulate the transcriptional trajectory of bone marrow hematopoietic progenitors into macrophage lineage commitment

Using a variety of differentiation-inducible myeloid cell lines, we previously showed that the zinc-finger transcription factor early growth response gene 1 (Egr-1) is a positive modulator of macrophage differentiation and negatively regulates granulocytic differentiation. In this study, high-efficiency retroviral transduction was used to ectopically express Egr-1 in myeloid-enriched or stem cell–enriched bone marrow cultures to explore its effect on the development of hematopoietic progenitors in vitro and in lethally irradiated mice. It was found that ectopic Egr-1 expression in normal hematopoietic progenitors stimulates development along the macrophage lineage at the expense of development along the granulocyte or erythroid lineages, regardless of the cytokine used. Moreover, Egr-1 accelerated macrophage development by suppressing the proliferative phase of the growth-to-macrophage developmental program. The remarkable ability of Egr-1 to dictate macrophage development at the expense of development along other lineages resulted in failure of Egr-1–infected hematopoietic progenitors to repopulate the bone marrow and spleen, and thereby prevent death, in lethally irradiated mice. These observations further highlight the role Egr-1 plays in monocytic differentiation and growth suppression.

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Molecular control of endothelial tube formation from single and aggregated cells by lumen signalling complexes that contain MT1-MMP and CDC42 in 3D collagen matrices

10.32469/10355/8432 ◽

2010 ◽

Author(s):

Anastasia Sacharidou

Keyword(s):

Tube Formation ◽

Collagen Matrices ◽

Molecular Control ◽

Endothelial Tube Formation ◽

3D Collagen

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Faculty Opinions recommendation of Bone marrow origin of hematopoietic progenitors and stem cells in murine muscle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1000541.12187 ◽

2001 ◽

Author(s):

Gerald Spangrude

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Progenitors ◽

Bone Marrow Origin

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Faculty Opinions recommendation of MT1-MMP- and Cdc42-dependent signaling co-regulate cell invasion and tunnel formation in 3D collagen matrices.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1282966.750068 ◽

2009 ◽

Author(s):

Jonathan Jones

Keyword(s):

Cell Invasion ◽

Collagen Matrices ◽

3D Collagen

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Relationship between Thy-1 expression and cell-cycle distribution in human bone marrow hematopoietic progenitors

American Journal of Hematology ◽

10.1002/ajh.20362 ◽

2005 ◽

Vol 79 (3) ◽

pp. 187-193 ◽

Cited By ~ 9

Author(s):

Hiroki Takeda ◽

Masuji Yamamoto ◽

Naoko Morita ◽

Takakuni Tanizawa

Keyword(s):

Cell Cycle ◽

Bone Marrow ◽

Human Bone ◽

Human Bone Marrow ◽

Cell Cycle Distribution ◽

Hematopoietic Progenitors

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Stromal-Dependent Hematopoietic Progenitors Permeate the CD45 CD31 Ter119 Bone Marrow Cell Fraction

Experimental Hematology ◽

10.1016/j.exphem.2018.06.066 ◽

2018 ◽

Vol 64 ◽

pp. S49-S50

Author(s):

Philip Boulais ◽

Toshihide Mizoguchi ◽

Samuel Zimmerman ◽

Fumio Nakahara ◽

Judith Vivié ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cell ◽

Marrow Cell ◽

Cell Fraction ◽

Hematopoietic Progenitors

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Endothelial lumen signaling complexes control 3D matrix–specific tubulogenesis through interdependent Cdc42- and MT1-MMP–mediated events

Blood ◽

10.1182/blood-2009-11-252692 ◽

2010 ◽

Vol 115 (25) ◽

pp. 5259-5269 ◽

Cited By ~ 90

Author(s):

Anastasia Sacharidou ◽

Wonshill Koh ◽

Amber N. Stratman ◽

Anne M. Mayo ◽

Kevin E. Fisher ◽

...

Keyword(s):

Tube Formation ◽

Dominant Negative ◽

Collagen Matrices ◽

Signaling Complex ◽

Vascular Morphogenesis ◽

Cytoplasmic Tails ◽

3D Matrix ◽

Dependent Signal ◽

3D Collagen ◽

Membrane Type

Abstract Here, we define an endothelial cell (EC) lumen signaling complex involving Cdc42, Par6b, Par3, junction adhesion molecule (Jam)–B and Jam-C, membrane type 1–matrix metalloproteinase (MT1-MMP), and integrin α2β1, which coassociate to control human EC tubulogenesis in 3D collagen matrices. Blockade of both Jam-B and Jam-C using antibodies, siRNA, or dominant-negative mutants completely interferes with lumen and tube formation resulting from a lack of Cdc42 activation, inhibition of Cdc42-GTP–dependent signal transduction, and blockade of MT1-MMP–dependent proteolysis. This process requires interdependent Cdc42 and MT1-MMP signaling, which involves Par3 binding to the Jam-B and Jam-C cytoplasmic tails, an interaction that is necessary to physically couple the components of the lumen signaling complex. MT1-MMP proteolytic activity is necessary for Cdc42 activation during EC tube formation in 3D collagen matrices but not on 2D collagen surfaces, whereas Cdc42 activation is necessary for MT1-MMP to create vascular guidance tunnels and tube networks in 3D matrices through proteolytic events. This work reveals a novel interdependent role for Cdc42-dependent signaling and MT1-MMP–dependent proteolysis, a process that occurs selectively in 3D collagen matrices and that requires EC lumen signaling complexes, to control human EC tubulogenesis during vascular morphogenesis.

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Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices

Microvascular Research ◽

10.1016/j.mvr.2015.06.006 ◽

2015 ◽

Vol 101 ◽

pp. 72-81 ◽

Cited By ~ 24

Author(s):

Hyojin Kim ◽

Nutan Prasain ◽

Sasidhar Vemula ◽

Michael J. Ferkowicz ◽

Momoko Yoshimoto ◽

...

Keyword(s):

Cord Blood ◽

Human Platelet ◽

Three Dimensional ◽

Platelet Lysate ◽

Human Cord Blood ◽

Collagen Matrices ◽

Human Platelet Lysate ◽

3D Collagen

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N-cadherin is developmentally regulated and functionally involved in early hematopoietic cell differentiation

Journal of Cell Science ◽

10.1242/jcs.114.8.1567 ◽

2001 ◽

Vol 114 (8) ◽

pp. 1567-1577 ◽

Cited By ~ 2

Author(s):

S. Puch ◽

S. Armeanu ◽

C. Kibler ◽

K.R. Johnson ◽

C.A. Muller ◽

...

Keyword(s):

Bone Marrow ◽

Cell Adhesion ◽

Progenitor Cells ◽

Mononuclear Cells ◽

Classical Type ◽

Type I ◽

Facs Analysis ◽

Hematopoietic Progenitors ◽

Developmentally Regulated ◽

Adhesive Interactions

The cadherins, an important family of cell adhesion molecules, are known to play major roles during embryonic development and in the maintenance of solid tissue architecture. In the hematopoietic system, however, little is known of the role of this cell adhesion family. By RT-PCR, western blot analysis and immunofluorescence staining we show that N-cadherin, a classical type I cadherin mainly expressed on neuronal, endothelial and muscle cells, is expressed on the cell surface of resident bone marrow stromal cells. FACS analysis of bone marrow mononuclear cells revealed that N-cadherin is also expressed on a subpopulation of early hematopoietic progenitor cells. Triple-color FACS analysis defined a new CD34(+) CD19(+) N-cadherin(+) progenitor cell population. During further differentiation, however, N-cadherin expression is lost. Treatment of CD34(+) progenitor cells with function-perturbing N-cadherin antibodies drastically diminished colony formation, indicating a direct involvement of N-cadherin in the differentiation program of early hematopoietic progenitors. N-cadherin can also mediate adhesive interactions within the bone marrow as demonstrated by inhibition of homotypic interactions of bone-marrow-derived cells with N-cadherin antibodies. Together, these data strongly suggest that N-cadherin is involved in the development and retention of early hematopoietic progenitors within the bone marrow microenvironment.

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