Endoglin Is Not Critical for Hematopoietic Stem Cell Engraftment and Reconstitution but Regulates Adult Erythroid Development

Moody, Jennifer L.; Singbrant, Sofie; Karlsson, Göran; Blank, Ulrika; Aspling, Marie; Flygare, Johan; Bryder, David; Karlsson, Stefán

doi:10.1634/stemcells.2006-0602

Cited by 19 publications

(29 citation statements)

References 49 publications

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“…27 Pre-stimulated stem and progenitor cellenriched bone marrow (BM) was cultured on retronectincoated plates (Takara Bioscience, Clontech) pre-loaded with viral supernatant (1-2 hits).…”

Section: Virus and Infectionsmentioning

confidence: 99%

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease

et al. 2014

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© F e r r a t a S t o r t i F o u n d a t i o nat B.R.C. St Vincent's Hospital, Australia. All experiments were performed under the ethical guidelines of the Lund University or St Vincent's Health Melbourne animal ethics committees. 0.1-5x10 5 unsorted transduced cells from C57Bl/6 mice (BalbC in Online Supplementary Figure S3) were injected intravenously (IV) with 1-2x10 5 fresh whole BM cells into lethally irradiated recipients (8-12 weeks old, tracked using CD45.1/CD45.2). Cells from multiple transductions (n>8 for MIG and SKI; n=3 for ARPG) were transplanted into 4-6 recipients/transduction. Recipients were sacrificed after 16 weeks and the equivalent of half a femur of BM was transplanted into secondary and tertiary recipients. One cohort of mice was kept for 18 months. Cell preparations and flow cytometryPeripheral blood (PB), BM and spleen were analyzed on a Sysmex (Boule Medonice CA 530-16, or Sysmex KX-21N, Roche Diagnostics, Australia). FACS analysis was performed on a FACS Calibur or LSRFortessa, while cell sorting was performed on a FACS Diva or FACS Aria (BD, San Jose, CA, USA). Results were analyzed with FlowJo software, v.8.8.6 (Tree Star, Ashland, OR, USA). Hematopoietic progenitor assaysTo analyze TGF-β sensitivity, 200 GFP+ cells/mL were seeded in methylcellulose (M3231, Stem Cell Technologies), supplemented with 50 ng/mL mSCF, 10 ng/mL mIL-3, and 10 ng/mL hIL-6, with or without 10 ng/mL TGF-β (all from PeproTech, Rocky Hill, NJ, USA) (n=2 transductions). Unsorted BM cells from 16 weeks post-transplantation were plated for colonies; 30,000 cells/mL as above for myeloid and 50,000 cells/mL for pre-B-cell colonies (M3630). For HGF-analysis 250 sorted GFP+ cells/mL were seeded in methylcellulose with 50 ng/mL mSCF, 10 ng/mL mIL-3, 50 ng/mL hIL6, and 3 U/mL rhEpo (Jansen-Cilag) together with 0, 100 nm or 300 nm of MET Inhibitor III (Calbiochem cat. n. 448105) (n=3 separate transductions). All colonies were scored on Day 7. MorphologyPB smears and BM cytospins were stained with May Grünwald (Merck) and Giemsa (BDH). Megakaryocytes were scored in paraffin-embedded sections of decalcified tibiae stained with Mayer's hematoxylin and eosin (n=4 for MIG; n=5 for SKI). Images were taken using an S. Singbrant et al. 648 haematologica | 2014; 99(4) © F e r r a t a S t o r t i F o u n d a t i o nOlympus BH2 microscope and a MagnaFire-SP Optronics Digital Camera. Gene expression profilingQuantification of RNA was made on GFP+ BM cells using the Taq-Man™ System (Applied Biosystems, Foster City, CA, USA). For microarray, total RNA was extracted from GFP+ LKS cells using the RNeasy Micro kit (Qiagen), and hybridized to the Illumina Mouse WG-6 v.2.0 Expression BeadChip at the Ramaciotti Centre for Gene Function Analysis, University of NSW, Australia (n=6 independent transductions). For Illumina data analysis see the Online Supplementary Methods, differentially expressed genes in Online Supplementary Appendix File 1, enriched gene sets in Online Supplementary Appendix File 2, and raw and processed mi...

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“…27 Pre-stimulated stem and progenitor cellenriched bone marrow (BM) was cultured on retronectincoated plates (Takara Bioscience, Clontech) pre-loaded with viral supernatant (1-2 hits).…”

Section: Virus and Infectionsmentioning

confidence: 99%

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease

et al. 2014

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“…However, transplantation of transduced BM enriched in primitive hematopoietic stem and progenitor cells reveals that neither endoglin suppression nor endoglin overexpression affects the ability of HSCs to repopulate recipient marrow in the short or long term. 69 …”

Section: 55mentioning

confidence: 99%

Complex and Context Dependent Regulation of Hematopoiesis by TGF‐β Superfamily Signaling

Söderberg

Karlsson

2009

Annals of the New York Academy of Sciences

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101

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The transforming growth factor (TGF)-β superfamily of growth factors, including the TGF-βs, activins, and bone morphogenetic proteins (BMPs), provide cells with a broad spectrum of regulatory signals through the intracellular Smad pathway. Since lossof-function studies of a majority of the TGF-β superfamily members result in embryonic lethality, much of our current knowledge of the TGF-β superfamily's role in hematopoiesis is generated from studies performed in vitro, or in very early stages of embryonic development. TGF-β is well documented as a potent inhibitor of hematopoietic stem cell (HSC) proliferation in vitro, while its role in vivo is largely unknown. BMP signaling is crucial for the initiation of hematopoiesis in the developing embryo, although its role in adult hematopoiesis remains elusive. More recently we and others have used conditional knockout models to unravel the role of several components of TGF-β family signaling in adult hematopoiesis. Here we review the currently known functions for the major factors of this signaling family in embryonic and adult hematopoietic regulation and discuss the context dependency and complexity that permeate this regulation.

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“…Anemia observed in patients with HHT1 and in Endoglin -/-mice is another indicator for a possible role of Endoglin in erythropoiesis. In the adult setting, in addition to its involvement in angiogenesis and vascular repair (Hayrabedyan et al, 2005;van Laake et al, 2006), Endoglin is expressed in long-term repopulating hematopoietic stem cells from bone marrow (Chen et al, 2002) and was reported to play a role in erythroid lineage differentiation (Moody et al, 2007). Increased levels of Endoglin expression were also found in tumors (Fonsatti et al, 2001), atherosclerotic plaques (Conley et al, 2000) and during inflammation and wound healing (Torsney et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of Endoglin, a TGF-beta co-receptor, during pre-circulation vascular development in chick

Alev¹,

McIntyre²,

Ota³

et al. 2010

Int. J. Dev. Biol.

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Endoglin Is Not Critical for Hematopoietic Stem Cell Engraftment and Reconstitution but Regulates Adult Erythroid Development

Cited by 19 publications

References 49 publications

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease

The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease

Complex and Context Dependent Regulation of Hematopoiesis by TGF‐β Superfamily Signaling

Dynamic expression of Endoglin, a TGF-beta co-receptor, during pre-circulation vascular development in chick

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