Project description:The tunica adventitia ensheaths arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells expresses the CD10/CALLA cell surface metalloprotease. Sorted CD10+ adventitial cells developed promptly in culture into MSCs, exhibiting higher proliferation, clonogenic and osteogenic potentials than CD10- counterparts. CD10+ adventitial cells increased expression of the cell cycle protein CCND2 via ERK1/2 and prompted NELL1 expression via NF-κB. CD10 expression was upregulated in CD10+ adventitial cells through neural secreted protein sonic hedgehog-mediated Gli1 signaling. These results suggest that CD10 expression, which marks rapidly dividing cells in other normal and malignant cell lineages, plays a role in MSC homeostasis in human tissues.
Project description:In order to find the difference between human lung tissue-derived fibroblasts and human vascular adventitial fibroblasts for enhancing tumor formation ablity of human lung adenocarcinoma cell line A549, we found that human vascular adventitial fibroblasts enhance A549 tumor formation in vivo compared to human lung tissue-derived fibroblasts. To find the responsible genes for this phenomena, we used microarray analysis to find the expression difference between lung tissue-derived fibroblasts and vascular adventitial fibroblas Cultured human lung tissue-derived fibroblasts and human vascular adventitial fibroblasts were analyzed in replicates.
Project description:In order to find the difference between human lung tissue-derived fibroblasts and human vascular adventitial fibroblasts for enhancing tumor formation ablity of human lung adenocarcinoma cell line A549, we found that human vascular adventitial fibroblasts enhance A549 tumor formation in vivo compared to human lung tissue-derived fibroblasts. To find the responsible genes for this phenomena, we used microarray analysis to find the expression difference between lung tissue-derived fibroblasts and vascular adventitial fibroblas
Project description:Analysis of effect of CD10 in melanoma at gene expression level. The hypothesis tested in the present study was that CD10 promotes melanoma tumor progression. Results provide important information of the significant gene expression change between CD10-transfected and mock-transfected A375 cells, such as significantly increased genes included those related to anti-apoptosis, angiogenesis and cell proliferation.
Project description:Studies of adult human hematopoiesis have until now relied on the expression of CD10 to define lymphoid commitment. We report a novel lymphoid-primed population in human bone marrow that is generated from hematopoietic stem cells (HSC) prior to the onset of CD10 expression and B cell commitment, and is identified by high levels of the homing molecule L-selectin (CD62L). CD10-CD62Lhi progenitors have full lymphoid (B/T/NK) potential, and show reduced myeloid and absent erythroid potential. Genome-wide gene expression analysis demonstrates that the CD10-CD62Lhi population represents an intermediate stage of differentiation between CD34+CD38- HSC and CD34+lin-CD10+ progenitors marked by down-regulation of TAL1 and MPL, upregulation of E2A, CD3E and IL2RG expression, and absent B cell commitment or RAG1/2 expression. Immature CD34+CD1a- thymocytes are also CD62Lhi and L-selectin ligands are expressed at the cortico-medullary junction, suggesting a possible role for L-selectin in human thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow.
Project description:Analysis of effect of CD10 in melanoma at gene expression level. The hypothesis tested in the present study was that CD10 promotes melanoma tumor progression. Results provide important information of the significant gene expression change between CD10-transfected and mock-transfected A375 cells, such as significantly increased genes included those related to anti-apoptosis, angiogenesis and cell proliferation. Total RNA obtained from CD10-transfected A375 melanoma cells was that from compared to mock-transfected A375 cells.
Project description:This study was designed to follow the transcriptome changes during BMP2 mediated transformation of the MCF10A human mammary stem cell model. We found that long-term BMP2/IL6 exposure of MCF10A cells, human immortalized but non-transformed mammary stem cells and progenitors, led to their luminal transformation. MC26 cells correspond to MCF10A cells transformed by BMP2/IL6 long-term exposure and contrarily to their parental cells, are able to engraft in immunodeficient mice and form colonies in soft-agar. M1B26 cells were obtained after BMP2/IL-6 long-term treatment of MCF10A cells sorted for high BMPR1B expression and subsequent isolation and expansion of 3 soft-agar colonies. M1B26 have an increased ability to engraft in mice and form colonies in soft-agar when compared to MC26 cells. As a non-transformed control, MCF10A-CT cells were kept in culture without BMP2/IL6 for the same length of time than MC26 cells. MCF10A-CT, MC26 and M1B26 cells are thus a model allowing to follow the molecular events associated with the initiation of a luminal transformation in mammary stem cells. Expression of the CD10 membrane endopeptidase has been associated with cancer although it can be a marker of both good or poor prognosis depending on the stage of the cancer and on the tissue of origin. In addition, we showed that CD10 was a marker of stem cell containing populations in healthy mammary tissue and that CD10 enzymatic activity was involved in the maintenance of cells immature properties. Having recently shown that CD10 expression was increasing during BMP2 mediated transformation and that CD10 expressing cells were more transformed but that CD10 was not required for transformation, we set out to determine the gene signature associated with CD10 expression.
Project description:Studies of adult human hematopoiesis have until now relied on the expression of CD10 to define lymphoid commitment. We report a novel lymphoid-primed population in human bone marrow that is generated from hematopoietic stem cells (HSC) prior to the onset of CD10 expression and B cell commitment, and is identified by high levels of the homing molecule L-selectin (CD62L). CD10-CD62Lhi progenitors have full lymphoid (B/T/NK) potential, and show reduced myeloid and absent erythroid potential. Genome-wide gene expression analysis demonstrates that the CD10-CD62Lhi population represents an intermediate stage of differentiation between CD34+CD38- HSC and CD34+lin-CD10+ progenitors marked by down-regulation of TAL1 and MPL, upregulation of E2A, CD3E and IL2RG expression, and absent B cell commitment or RAG1/2 expression. Immature CD34+CD1a- thymocytes are also CD62Lhi and L-selectin ligands are expressed at the cortico-medullary junction, suggesting a possible role for L-selectin in human thymic homing. These studies identify the earliest stage of lymphoid priming in human bone marrow. Freshly harvested human bone marrow was ficoll purified, enriched for CD34+, and then FACS sorted. It was then sorted into 3 samples CD34+CD38-, CD34+ CD10- CD62L++, and CD34+ CD10+, with 3 independent biological replicates
Project description:We report differentially expressed genes in human pulmonary arterial adventitial fibroblasts under genotoxic stress (Doxorubicin) or pharmacological p53-activation by Nutlin-3.