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Qian, Hong
Publications (10 of 17) Show all publications
Vasilache, A.-M., Qian, H. & Blomqvist, A. (2015). Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling. Brain, behavior, and immunity, 48, 31-41
Open this publication in new window or tab >>Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling
2015 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 48, p. 31-41Article in journal (Refereed) Published
Abstract [en]

The cells constituting the blood-brain barrier are critical for the transduction of peripheral immune signals to the brain, but hitherto no comprehensive analysis of the signaling events that occur in these cells in response to a peripheral inflammatory stimulus has been performed. Here, we examined the inflammatory transcriptome in blood-brain barrier cells, including endothelial cells, pericytes, and perivascular macrophages, which were isolated by fluorescent-activated cell sorting, from non-immune-challenged mice and from mice stimulated by bacterial wall lipopolysaccharide. We show that endothelial cells and perivascular macrophages display distinct transcription profiles for inflammatory signaling and respond in distinct and often opposing ways to the immune stimulus. Thus, endothelial cells show induced PGE2 synthesis and transport with attenuation of PGE2 catabolism, increased expression of cytokine receptors and down-stream signaling molecules, and downregulation of adhesion molecules. In contrast, perivascular macrophages show downregulation of the synthesis of prostanoids other than PGE2 and of prostaglandin catabolism, but upregulation of interleukin-6 synthesis. Pericytes were largely unresponsive to the immune stimulation, with the exception of downregulation of proteins involved in pericyte-endothelial cell communication. While the endothelial cells account for most of the immune-induced gene expression changes in the blood-brain barrier, the response of the endothelial cells occurs in a concerted manner with that of the perivascular cells to elevate intracerebral levels of PGE2, hence emphasizing the critical role of PGE2 in immune-induced signal transduction across the blood-brain barrier.

Place, publisher, year, edition, pages
Academic Press, 2015
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114377 (URN)10.1016/j.bbi.2015.02.003 (DOI)000358460700005 ()25678162 (PubMedID)
Note

This work was supported by Grants from the Swedish Research Council (07879 to AB, and 22241 to HQ), the Swedish Cancer Foundation (13 0295 to AB), the Swedish Brain Foundation (to AB), the County Council of Ostergotland (to AMV), and Knut och Alice Wallenberg Foundation (WIRM to HQ).

Available from: 2015-02-19 Created: 2015-02-19 Last updated: 2018-01-11Bibliographically approved
Åhsberg, J., Ungerbäck, J., Strid, T., Welinder, E., Stjernberg, J., Larsson, M., . . . Sigvardsson, M. (2013). Early B-cell Factor 1 Regulates the Expansion of B-cell Progenitors in a Dose-dependent Manner. Journal of Biological Chemistry, 288(46), 33449-33461
Open this publication in new window or tab >>Early B-cell Factor 1 Regulates the Expansion of B-cell Progenitors in a Dose-dependent Manner
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2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 46, p. 33449-33461Article in journal (Refereed) Published
Abstract [en]

Transcription factor doses are of importance for normal and malignant B-lymphocyte development; however, the understanding of underlying mechanisms and functional consequences of reduced transcription factor levels is limited. We have analyzed progenitor and B-lineage compartments in mice carrying heterozygote mutations in the E2a, Ebf1, or Pax5 gene. Although lymphoid progenitors from Ebf1 or Pax5 heterozygote mice were specified and lineage-restricted in a manner comparable with Wt progenitors, this process was severely impaired in E2a heterozygote mutant mice. This defect was not significantly enhanced upon combined deletion of E2a with Ebf1 or Pax5. Analysis of the pre-B-cell compartment in Ebf1 heterozygote mice revealed a reduction in cell numbers. These cells expressed Pax5 and other B-lineage-associated genes, and global gene expression analysis suggested that the reduction of the pre-B-cell compartment was a result of impaired pre-B-cell expansion. This idea was supported by a reduction in IL2R-expressing late pre-B-cells as well as by cell cycle analysis and by the finding that the complexity of the VDJ rearrangement patterns was comparable in Wt and Ebf1(+/-) pre-B-cells, although the number of progenitors was reduced. Heterozygote deletion of Ebf1 resulted in impaired response to IL7 in vitro and reduced expression levels of pre-BCR on the cell surface, providing possible explanations for the observed stage-specific reduction in cellular expansion. Thus, transcription factor doses are critical for specification as well as expansion of B-lymphoid progenitors, providing increased insight into the molecular regulation of B-cell development.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2013
Keywords
Development; Differentiation; Immunology; Lymphocyte; Transcription Factors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103303 (URN)10.1074/jbc.M113.506261 (DOI)000328841700057 ()
Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2019-02-11
Man Wong, W., Sigvardsson, M., Astrand-Grundstrom, I., Hogge, D., Larsson, J., Qian, H. & Ekblom, M. (2013). Expression of Integrin alpha 2 Receptor in Human Cord Blood CD34+CD38-CD90+Stem Cells Engrafting Long-Term in NOD/SCID-IL2R gamma(c)null Mice. Stem Cells, 31(2), 360-371
Open this publication in new window or tab >>Expression of Integrin alpha 2 Receptor in Human Cord Blood CD34+CD38-CD90+Stem Cells Engrafting Long-Term in NOD/SCID-IL2R gamma(c)null Mice
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2013 (English)In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 31, no 2, p. 360-371Article in journal (Refereed) Published
Abstract [en]

Human hematopoietic stem cells reside in the CD34+CD38-CD90+ population in cord blood and bone marrow. However, this cell fraction is heterogeneous, and the phenotype of the rare primitive stem cells remains poorly defined. We here report that primitive cord blood CD34+CD38-CD90+ stem cells, with the ability to reconstitute NOD/SCID-IL2R gamma(c)null (NSG) mice long-term, at 24 weeks after transplantation, can be prospectively isolated at an increased purity by using integrin alpha 2 receptor as an additional stem cell marker. Using a limiting dilution transplantation assay, we found a highly significant enrichment of multilineage reconstituting stem cells in the CD34+CD38-CD90+ cell fraction expressing the integrin alpha 2 receptor, with a frequency of 1/29 cells, as compared to a frequency of 1/157 in the corresponding integrin alpha 2- cells. In line with this, long-term reconstituting stem cells within the cord blood CD34+CD38- cell population were significantly enriched in the integrin alpha 2+ fraction, while stem cells and progenitors reconstituting short-term, at 8-12 weeks, were heterogeneous in integrin alpha 2 expression. Global gene expression profiling revealed that the lineage-marker negative (Lin-) CD34+CD38-CD90+CD45RA- integrin alpha 2+ cell population was molecularly distinct from the integrin alpha 2- cell population and the more mature Lin-CD34+CD38-CD90-CD45RA- cell population. Our findings identify integrin alpha 2 as a novel stem cell marker, which improves prospective isolation of the primitive human hematopoietic stem cells within the CD34+CD38-CD90+ cell population for experimental and therapeutic stem cell applications. STEM CELLS 2013;31:360-371

Place, publisher, year, edition, pages
AlphaMed Press, 2013
Keywords
Hematopoietic stem cells, Fetal blood, Integrin alpha2, Human
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90073 (URN)10.1002/stem.1282 (DOI)000314873000015 ()
Note

Funding Agencies|Swedish Cancer Society|CAN 2010/590CAN 2009/1589|Swedish Research Council|2008-19616-59131-19K2008-77PK-20879-01-2|Medical Faculty, Lund University||Skane University Hospital||Gunnar Nilsson Foundation||John Persson Foundation||Gunnel Bjork Foundation||Georg Danielsson Foundation||Karolinska Institute Wallenberg Institute for Regenerative Medicine||

Available from: 2013-03-21 Created: 2013-03-19 Last updated: 2017-12-06
Qian, H., Badaloni, A., Chiara, F., Stjernberg, J., Polisetti, N., Nihlberg, K., . . . Sigvardsson, M. (2013). Molecular Characterization of Prospectively Isolated Multipotent Mesenchymal Progenitors Provides New Insight into the Cellular Identity of Mesenchymal Stem Cells in Mouse Bone Marrow. Molecular and Cellular Biology, 33(4), 661-677
Open this publication in new window or tab >>Molecular Characterization of Prospectively Isolated Multipotent Mesenchymal Progenitors Provides New Insight into the Cellular Identity of Mesenchymal Stem Cells in Mouse Bone Marrow
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2013 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 33, no 4, p. 661-677Article in journal (Refereed) Published
Abstract [en]

Despite great progress in the identification of mesenchymal stem cells (MSCs) from bone marrow (BM), our knowledge of their in vivo cellular identity remains limited. We report here that cells expressing the transcription factor Ebf2 in adult BM display characteristics of MSCs. The Ebf2(+) cells are highly clonal and physiologically quiescent. In vivo lineage-tracing experiments, single cell clone transplantations, and in vitro differentiation assays revealed their self-renewal and multilineage differentiation capacity. Gene expression analysis of the freshly sorted Ebf2(+) cells demonstrated the expression of genes previously reported to be associated with MSCs and the coexpression of multiple lineage-associated genes at the single-cell level. Thus, Ebf2 expression is not restricted to committed osteoblast progenitor cells but rather marks a multipotent mesenchymal progenitor cell population in adult mouse BM. These cells do not appear to completely overlap the previously reported MSC populations. These findings provide new insights into the in vivo cellular identity and molecular properties of BM mesenchymal stem and progenitor cells.

Place, publisher, year, edition, pages
American Society for Microbiology, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-92619 (URN)10.1128/MCB.01287-12 (DOI)000317267000002 ()
Note

Funding Agencies|Swedish Research Council|K2008-77PK-20879-01-22009-2675|Cancer-fonden|CAN 2009/1589CAN 2012-2015|AFA Insurance Regenerative Medicine Program||Faculty of Medicine at Linkoping University||

Available from: 2013-05-16 Created: 2013-05-14 Last updated: 2019-02-11
Sigvardsson, M., Zandi, S., Åhsberg, J., Qian, H. & Stjenrberg, J. (2012). Distinct regulatory networks control B-lymphoid specification and lineage commitment in JOURNAL OF IMMUNOLOGY, vol 188, issue , pp. In: JOURNAL OF IMMUNOLOGY. American Association of Immunologists, 188
Open this publication in new window or tab >>Distinct regulatory networks control B-lymphoid specification and lineage commitment in JOURNAL OF IMMUNOLOGY, vol 188, issue , pp
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2012 (English)In: JOURNAL OF IMMUNOLOGY, American Association of Immunologists , 2012, Vol. 188Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
American Association of Immunologists, 2012
Series
JOURNAL OF IMMUNOLOGY, ISSN 1550-6606
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-78818 (URN)000304659700476 ()
Available from: 2012-06-21 Created: 2012-06-21 Last updated: 2012-06-21
Engström, L., Ruud, J., Eskilsson, A., Larsson, A., Mackerlova, L., Kugelberg, U., . . . Blomqvist, A. (2012). Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells. Endocrinology, 153(10), 4849-4861
Open this publication in new window or tab >>Lipopolysaccharide-Induced Fever Depends on Prostaglandin E2 Production Specifically in Brain Endothelial Cells
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2012 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 153, no 10, p. 4849-4861Article in journal (Refereed) Published
Abstract [en]

Immune-induced prostaglandin E2 (PGE2) synthesis is critical for fever and other centrally elicited disease symptoms. The production of PGE2 depends on cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES-1), but the identity of the cells involved has been a matter of controversy. We generated mice expressing mPGES-1 either in cells of hematopoietic or nonhematopoietic origin. Mice lacking mPGES-1 in hematopoietic cells displayed an intact febrile response to lipopolysaccharide, associated with elevated levels of PGE2 in the cerebrospinal fluid. In contrast, mice that expressed mPGES-1 only in hematopoietic cells, although displaying elevated PGE2 levels in plasma but not in the cerebrospinal fluid, showed no febrile response to lipopolysaccharide, thus pointing to the critical role of brain-derived PGE2 for fever. Immunohistochemical stainings showed that induced cyclooxygenase-2 expression in the brain exclusively occurred in endothelial cells, and quantitative PCR analysis on brain cells isolated by flow cytometry demonstrated that mPGES-1 is induced in endothelial cells and not in vascular wall macrophages. Similar analysis on liver cells showed induced expression in macrophages and not in endothelial cells, pointing at the distinct role for brain endothelial cells in PGE2 synthesis. These results identify the brain endothelial cells as the PGE2-producing cells critical for immune-induced fever.

Place, publisher, year, edition, pages
Endocrine Society, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84885 (URN)10.1210/en.2012-1375 (DOI)000309210200027 ()
Note

Funding Agencies|Swedish Research Council|7879|Swedish Cancer Foundation|100533|Swedish Brain Foundation||Gustav V:s 80-ars Fond||

Available from: 2012-11-01 Created: 2012-10-26 Last updated: 2017-12-07
Qian, H., Le Blanc, K. & Sigvardsson, M. (2012). Primary Mesenchymal Stem and Progenitor Cells from Bone Marrow Lack Expression of CD44 Protein. Journal of Biological Chemistry, 287(31), 25795-25807
Open this publication in new window or tab >>Primary Mesenchymal Stem and Progenitor Cells from Bone Marrow Lack Expression of CD44 Protein
2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 31, p. 25795-25807Article in journal (Refereed) Published
Abstract [en]

Despite significant progress in our understanding of mesenchymal stem cell (MSC) biology during recent years, much of the information is based on experiments using in vitro culture-selected stromal progenitor cells. Therefore, the natural cellular identity of MSCs remains poorly defined. Numerous studies have reported that CD44 expression is one of the characteristics of MSCs in both humans and mice; however, we here have prospectively isolated bone marrow stromal cell subsets from both human and mouse bone marrow by flow cytometry and characterized them by gene expression analysis and function assays. Our data provide functional and molecular evidence suggesting that primary mesenchymal stem and progenitor cells of bone marrow reside in the CD44(-) cell fraction in both mice and humans. The finding that these CD44(-) cells acquire CD44 expression after in vitro culture provides an explanation for the previous misconceptions concerning CD44 expression on MSCs. In addition, the other previous reported MSC markers, including CD73, CD146, CD271, and CD106/VCAM1, are also differentially expressed on those two cell types. Our microarray data revealed a distinct gene expression profile of the freshly isolated CD44(-) cells and the cultured MSCs generated from these cells. Thus, we conclude that bone marrow MSCs physiologically lack expression of CD44, highlighting the natural phenotype of MSCs and opening new possibilities to prospectively isolate MSCs from the bone marrow.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80787 (URN)10.1074/jbc.M112.339622 (DOI)000306916300010 ()
Note

Funding Agencies|Swedish Cancer Society||Swedish Research Council||Swedish Childhood Cancer Foundation||Faculty of Medicine at Linkoping University||

Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2017-12-07
Zandi, S., Åhsberg, J., Tsapogas, P., Stjernberg, J., Qian, H. & Sigvardsson, M. (2012). Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo. Proceedings of the National Academy of Sciences of the United States of America, 109(39), 15871-15876
Open this publication in new window or tab >>Single-cell analysis of early B-lymphocyte development suggests independent regulation of lineage specification and commitment in vivo
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2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 39, p. 15871-15876Article in journal (Refereed) Published
Abstract [en]

To better understand the process of B-lymphocyte lineage restriction, we have investigated molecular and functional properties in early B-lineage cells from Pax-5-deficient animals crossed to a B-lineage-restricted reporter mouse, allowing us to identify B-lineage-specified progenitors independently of conventional surface markers. Pax-5 deficiency resulted in a dramatic increase in the frequency of specified progenitor B-cellsmarked by expression of a lambda 5 (Igll1) promoter-controlled reporter gene. Gene expression analysis of ex vivo isolated progenitor cells revealed that Pax-5 deficiency has a minor impact on B-cell specification. However, single-cell in vitro differentiation analysis of ex vivo isolated cells revealed that specified B-lineage progenitors still displayed a high degree of plasticity for development into NK or T lineage cells. In contrast, we were unable to detect any major changes in myeloid lineage potential in specified Pax-5-deficient cells. By comparison of gene expression patterns in ex vivo isolated Pax-5-and Ebf-1-deficient progenitors, it was possible to identify a set of B-cell-restricted genes dependent on Ebf-1 but not Pax-5, supporting the idea that B-cell specification and commitment is controlled by distinct regulatory networks.

Place, publisher, year, edition, pages
National Academy of Sciences, 2012
Keywords
transcription, Notch-1, Deltex
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85090 (URN)10.1073/pnas.1210144109 (DOI)000309604500070 ()
Note

Funding Agencies|Swedish Cancer Society||Swedish Research Council||Swedish Childhood Cancer Foundation||faculty of Medicine at Linkoping University||

Available from: 2012-11-02 Created: 2012-11-02 Last updated: 2017-12-07
Qian, H., Badaloni, A., Chiara, F., Zetterblad, J., Nihlberg, K., Consalez, G. & Sigvardsson, M. (2011). EBF2-EXPRESSING CELLS REPRESENT A HIGHLY PURIFIED MESENCHYMAL STEM CELL POPULATION IN ADULT MOUSE BONE MARROW in EXPERIMENTAL HEMATOLOGY, vol 39, issue 8, pp S109-S109. In: EXPERIMENTAL HEMATOLOGY (pp. S109-S109). Elsevier, 39(8)
Open this publication in new window or tab >>EBF2-EXPRESSING CELLS REPRESENT A HIGHLY PURIFIED MESENCHYMAL STEM CELL POPULATION IN ADULT MOUSE BONE MARROW in EXPERIMENTAL HEMATOLOGY, vol 39, issue 8, pp S109-S109
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2011 (English)In: EXPERIMENTAL HEMATOLOGY, Elsevier , 2011, Vol. 39, no 8, p. S109-S109Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70224 (URN)000293801700181 ()
Available from: 2011-08-26 Created: 2011-08-26 Last updated: 2011-08-26
Tsapogas, P., Zandi, S., Åhsberg, J., Zetterblad, J., Welinder, E., Jönsson, J.-I., . . . Sigvardsson, M. (2011). IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors. Blood, 118(5), 1283-1290
Open this publication in new window or tab >>IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors
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2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 5, p. 1283-1290Article in journal (Refereed) Published
Abstract [en]

eficiencies in the IL-7 signaling pathway result in severe disruptions of lymphoid development in adult mice. To understand more about how IL-7 deficiency impacts early lymphoid development, we have investigated lineage restriction events within the common lymphoid progenitor (CLP) compartment in IL-7 knockout mice. This revealed that although IL-7 deficiency had a minor impact on the development of LY6D(-) multipotent CLPs, the formation of the lineage restricted LY6D(+) CLP population was dramatically reduced. This was reflected in a low-level transcription of B-lineage genes as well as in a loss of functional B-cell commitment. The few Ly6D(+) CLPs developed in the absence of IL-7 displayed increased lineage plasticity and low expression of Ebf-1. Absence of Ebf-1 could be linked to increased plasticity because even though Ly6D(+) cells develop in Ebf-1-deficient mice, these cells retain both natural killer and dendritic cell potential. This reveals that IL-7 is essential for normal development of Ly6D(+) CLPs and that Ebf-1 is crucial for lineage restriction in early lymphoid progenitors.

Place, publisher, year, edition, pages
American Society of Hematology, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70104 (URN)10.1182/blood-2011-01-332189 (DOI)000293510000020 ()
Available from: 2011-08-19 Created: 2011-08-19 Last updated: 2017-12-08
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