62 results found
Barrett O, Sottocornola R, Lo Celso C, 2012, In vivo imaging of hematopoietic stem cells in the bone marrow niche., Methods Mol Biol, Vol: 916, Pages: 231-242
Even though hematopoietic stem cells (HSC) are amongst the first somatic stem cells exploited for therapeutic purposes, their application is still limited by the inability to expand them ex vivo without impairing their function. Moreover, it has recently emerged that several types of leukemia develop and relapse through complex interactions with bone marrow (BM) components and may directly affect the HSC and their niche. Increasing attention has therefore been dedicated to the BM microenvironment the HSC reside in, with the view that a better understanding of the molecular regulators of HSC-niche interaction in vivo will allow improving HSC mobilization, collection and transplantation and provide clues for the development of innovative leukemia treatments. This chapter focuses on a recently established technique for the visualization of transplanted hematopoietic stem and progenitor cells (HSPC) within the calvarium bone marrow of live mice (Lo Celso et al. Nature 457:92-96, 2007). Intravital microscopy is a rapidly developing field, driven by constant improvement in both detection technologies (i.e., spatial resolution, depth of penetration, spectral definition) and probe availability (i.e., increasingly sophisticated genetic and chemical reporter systems). We therefore discuss the current limitations and challenges related to intravital microscopy of the HSC niche and introduce a number of potential imaging approaches, which could be promising candidates for future development of this technique.
Sottocornola R, Lo Celso C, 2012, Dormancy in the stem cell niche, STEM CELL RESEARCH & THERAPY, Vol: 3, ISSN: 1757-6512
Cornejo MG, Mabialah V, Sykes SM, et al., 2011, Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification, BLOOD, Vol: 118, Pages: 1264-1273, ISSN: 0006-4971
Fujisaki J, Wu J, Carlson AL, et al., 2011, In vivo imaging of T-reg cells providing immune privilege to the haematopoietic stem-cell niche, NATURE, Vol: 474, Pages: 216-U256, ISSN: 0028-0836
Lane SW, Wang YJ, Lo Celso C, et al., 2011, Differential niche and Wnt requirements during acute myeloid leukemia progression, BLOOD, Vol: 118, Pages: 2849-2856, ISSN: 0006-4971
Lo Celso C, Lin CP, Scadden DT, 2011, In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow, NATURE PROTOCOLS, Vol: 6, Pages: 1-14, ISSN: 1754-2189
Lo Celso C, Scadden DT, 2011, The haematopoietic stem cell niche at a glance, JOURNAL OF CELL SCIENCE, Vol: 124, Pages: 3529-3535, ISSN: 0021-9533
Rodriguez S, Wang L, Mumaw C, et al., 2011, The SKP2 E3 ligase regulates basal homeostasis and stress-induced regeneration of HSCs, BLOOD, Vol: 117, Pages: 6509-6519, ISSN: 0006-4971
Sanchez-Aguilera A, Lee Y-J, Lo Celso C, et al., 2011, Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 9607-9612, ISSN: 0027-8424
Silberstein L, Osawa M, Lin C, et al., 2011, Real-Time RT-PCR Analysis of Individual Osteolineage Cells within the Hematopoietic Stem Cell Niche, 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis, Publisher: AMER SOC HEMATOLOGY, Pages: 1028-1029, ISSN: 0006-4971
Strydom N, Lo Celso C, Scott M, et al., 2011, Using intravital microscopy to investigate the molecules that regulate the homing of senescent neutrophils to the bone marrow and their phagocytosis by bone marrow macrophages, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 127-127, ISSN: 0019-2805
Ferraro F, Celso CL, Scadden D, 2010, Adult stem cels and their niches., Adv Exp Med Biol, Vol: 695, Pages: 155-168, ISSN: 0065-2598
Stem cells participate in dynamic physiologic systems that dictate the outcome of developmental events and organismal stress, Since these cells are fundamental to tissue maintenance and repair, the signals they receive play a critical role in the integrity of the organism. Much work has focused on stem cell identification and the molecular pathways involved in their regulation. Yet, we understand little about how these pathways achieve physiologically responsive stem cell functions. This chapter will review the state of our understanding of stem cells in the context of their microenvironment regarding the relation between stem cell niche dysfunction, carcinogenesis and aging.
Lane SW, Sykes SM, Al-Shahrour F, et al., 2010, The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS., Blood, Vol: 115, Pages: 3489-3497
Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. Analysis of the hematopoietic system of mice with the Apc(min) allele that results in a premature stop codon and loss of function showed no abnormality in steady state hematopoiesis. Bone marrow derived from Apc(min) mice showed enhanced repopulation potential, indicating a cell intrinsic gain of function in the long-term hematopoietic stem cell (HSC) population. However, Apc(min) bone marrow was unable to repopulate secondary recipients because of loss of the quiescent HSC population. Apc(min) mice developed a MDS/myeloproliferative phenotype. Our data indicate that Wnt activation through haploinsufficiency of Apc causes insidious loss of HSC function that is only evident in serial transplantation strategies. These data provide a cautionary note for HSC-expansion strategies through Wnt pathway activation, provide evidence that cell extrinsic factors can contribute to the development of myeloid disease, and indicate that loss of function of APC may contribute to the phenotype observed in patients with MDS and del(5q).
Lane SW, Sykes SM, Ferraro F, et al., 2010, LEUKEMIA STEM CELLS OCCUPY NICHES THAT ARE PHYSICALLY DISTINCT AND INDEPENDENT OF THE NORMAL CONSTRAINTS THAT APPLY TO HEMATOPOIETIC STEM CELLS, 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells, Publisher: ELSEVIER SCIENCE INC, Pages: S38-S38, ISSN: 0301-472X
Lo Celso C, 2010, Every cloud has a silver lining, BLOOD, Vol: 115, Pages: 438-439, ISSN: 0006-4971
Sanchez-Aguilera A, Lee Y-J, Lo Celso C, et al., 2010, Vav1 Regulates Perivascular Homing, Bone Marrow Retention and Engraftment of Hematopoietic Stem Cells Via SDF1a Signaling, 52nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, Pages: 179-179, ISSN: 0006-4971
Adams GB, Alley IR, Chung U-I, et al., 2009, Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow., Nature, Vol: 459, Pages: 103-107
Haematopoietic stem and progenitor cells (HSPCs) change location during development and circulate in mammals throughout life, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention. Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the guanine-nucleotide-binding protein stimulatory alpha subunit (Galpha(s)). HSPCs from adult mice deficient in Galpha(s) (Galpha(s)(-/-)) differentiate and undergo chemotaxis, but also do not home to or engraft in the bone marrow in adult mice and demonstrate a marked inability to engage the marrow microvasculature. If deleted after engraftment, Galpha(s) deficiency did not lead to lack of retention in the marrow, rather cytokine-induced mobilization into the blood was impaired. Testing whether activation of Galpha(s) affects HSPCs, pharmacological activators enhanced homing and engraftment in vivo. Galpha(s) governs specific aspects of HSPC localization under physiological conditions in vivo and may be pharmacologically targeted to improve transplantation efficiency.
Lo Celso C, Fleming HE, Wu JW, et al., 2009, Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche, NATURE, Vol: 457, Pages: 92-U96, ISSN: 0028-0836
Lo Celso C, Wu JW, Lin CP, 2009, In vivo imaging of hematopoietic stem cells and their microenvironment, JOURNAL OF BIOPHOTONICS, Vol: 2, Pages: 619-631, ISSN: 1864-063X
Fleming HE, Janzen V, Lo Celso C, et al., 2008, Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo, CELL STEM CELL, Vol: 2, Pages: 274-283, ISSN: 1934-5909
Janzen V, Fleming HE, Riedt T, et al., 2008, Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3, CELL STEM CELL, Vol: 2, Pages: 584-594, ISSN: 1934-5909
Lo Celso C, Berta MA, Braun KM, et al., 2008, Characterization of bipotential epidermal progenitors derived from human sebaceous gland: Contrasting roles of c-Myc and beta-catenin, STEM CELLS, Vol: 26, Pages: 1241-1252, ISSN: 1066-5099
Szotek PP, Chang HL, Brennand K, et al., 2008, Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 105, Pages: 12469-12473, ISSN: 0027-8424
Lo Celso C, Klein RJ, Scadden DT, 2007, Analysis of the hematopoietic stem cell niche., Curr Protoc Stem Cell Biol, Vol: Chapter 2, Pages: Unit-2A.5
Hematopoietic stem cells (HSCs) continuously replenish all blood cell lineages not only to maintain the normal rapid turnover of differentiated cells but also to respond to injury and stress. Cell-extrinsic mechanisms are critical determinants of the fine balance between HSC self-renewal and differentiation. The bone marrow microenvironment has emerged as a new area of intense study to identify which of its many components constitute the HSC niche and regulate HSC fate. While HSCs have been isolated, characterized and used in clinical practice for many years thanks to the development of very specific assays and technology (i.e., bone marrow transplants and fluorescence activated cell sorting), study of the HSC niche has evolved by combining experimental designs developed in different fields. In this unit we describe a collection of protocols spanning a wide range of techniques that can help every researcher tackling questions regarding the nature of the HSC niche.
Lo Celso C, Scadden D, 2007, Isolation and transplantation of hematopoietic stem cells (HSCs)., J Vis Exp
Lo Celso C, Scadden DT, 2007, Stem cells remember their grade, CELL STEM CELL, Vol: 1, Pages: 132-134, ISSN: 1934-5909
Estrach S, Ambler CA, Lo Celso C, et al., 2006, Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis., Development, Vol: 133, Pages: 4427-4438, ISSN: 0950-1991
The Wnt and Notch signalling pathways regulate hair follicle maintenance, but how they intersect is unknown. We show that Notch signalling is active in the hair follicle pre-cortex, a region of high Wnt activity, where commitment to hair lineages occurs. Deletion of jagged 1 (Jag1) results in inhibition of the hair growth cycle and conversion of hair follicles into cysts of cells undergoing interfollicular epidermal differentiation. Conversely, activation of Notch in adult epidermis triggers expansion of the base of the hair follicle, sebaceous gland enlargement and abnormal clumping of the follicles. In adult epidermis, the induction of new hair follicle formation by beta-catenin is prevented by blocking Notch signalling pharmacologically or through Jag1 deletion. Conversely, activation of both pathways accelerates growth and differentiation of ectopic follicles. beta-catenin stimulates Notch signalling by inducing Jag1 transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta-catenin pathway to determine epidermal cell fate.
Morita K, Lo Celso C, Spencer-Dene B, et al., 2006, HAN11 binds mDia1 and controls GLI1 transcriptional activity, JOURNAL OF DERMATOLOGICAL SCIENCE, Vol: 44, Pages: 11-20, ISSN: 0923-1811
Watt FM, Lo Celso C, Silva-Vargas V, 2006, Epidermal stem cells: an update, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 16, Pages: 518-524, ISSN: 0959-437X
Silva-Vargas V, Lo Celso C, Giangreco A, et al., 2005, Beta-catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells., Dev Cell, Vol: 9, Pages: 121-131, ISSN: 1534-5807
Using K14deltaNbeta-cateninER transgenic mice, we show that short-term, low-level beta-catenin activation stimulates de novo hair follicle formation from sebaceous glands and interfollicular epidermis, while only sustained, high-level activation induces new follicles from preexisting follicles. The Hedgehog pathway is upregulated by beta-catenin activation, and inhibition of Hedgehog signaling converts the low beta-catenin phenotype to wild-type epidermis and the high phenotype to low. beta-catenin-induced follicles contain clonogenic keratinocytes that express bulge markers; the follicles induce dermal papillae and provide a niche for melanocytes, and they undergo 4OHT-dependent cycles of growth and regression. New follicles induced in interfollicular epidermis are derived from that cellular compartment and not through bulge stem cell migration or division. These results demonstrate the remarkable capacity of adult epidermis to be reprogrammed by titrating beta-catenin and Hedgehog signal strength and establish that cells from interfollicular epidermis can acquire certain characteristics of bulge stem cells.
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