PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2014
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| Schlagworte: | |
| Online-Zugang: | kostenfrei Inhaltsverzeichnis |
| Beschreibung: | Online erschienen 2015 |
| Beschreibung: | 108 Bl. Ill., graph. Darst. |
Internformat
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| 245 | 1 | 0 | |a PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells |c von Linda Varagnolo |
| 246 | 1 | 3 | |a Die Inhibition des PRC2 wirkt dem Kultur-bedingten Verlust des Repopulationspotenzials in humanen hämatopoetischen Stammzellen/Vorläuferzellen aus Nabelschnurblut entgegen |
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Datensatz im Suchindex
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| adam_text | PRC2 INHIBITION COUNTERACTS
THE CULTURE-ASSOCIATED LOSS OF
ENGRAFTMENT POTENTIAL OF HUMAN
CORD BLOOD-DERIVED HEMATOPOIETIC
STEM/PROGENITOR CELLS
DIE INHIBITION DES PRC2 WIRKT
DEM KULTUR-BEDINGTEN VERLUST
DES REPOPULATIONSPOTENZIALS
IN HUMANEN HAMATOPOETISCHEN
STAMMZELLEN/VORLAUFERZELLEN AUS
NABELSCHNURBLUT ENTGEGEN
DOCTORAL THESIS FOR A DOCTORAL DEGREE
AT THE JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG,
SUBMITTED BY
LINDA VARAGNOLO
FROM
CHIOGGIA, ITALY
WURZBURG 2014
HTTP://D-NB.INFO/1066683417
TABLE OF CONTENTS
T
ABLE OF
C
ONTENTS
1 SUMMARY 9
2 ZUSAMMENFASSUNG 11
3 ABBREVIATIONS 13
4 INTRODUCTION 16
4.1 HEMATOPOIESIS 16
4.1.1 HEMATOPOIETIC STEM CELL 16
4.1.2 HSC TRANSPLANTATION (HSCT) 18
4.1.3 SOURCES OF HSCS FOR TRANSPLANTATION 19
4.1.4 UMBILICAL CORD BLOOD AS SOURCE OF HSCS 19
4.1.5 EXPANSION STRATEGIES 21
4.1.6 CYTOKINE-BASED EX VIVO EXPANSION 22
4.2 EPIGENETICS 23
4.2.1 BIVALENT DOMAINS 24
4.2.2 EPIGENETIC REGULATION OF HEMATOPOIESIS 25
4.2.3 EZH2 IN HEMATOPOIESIS 27
4.3 AIM AND EXPERIMENTAL STRATEGY 28
5 RESULTS 29
5.1 MORPHOLOGICAL AND IMMUNOPHENOTYPIC CHANGES UPON EXPANSION
OF HUMAN CB-CD34
+
CELLS 29
5.2 NSG TRANSPLANTATION OF EXPANDED CB-CD34
+
CELLS WITH DIFFERENT
CYTOKINE COMBINATIONS 31
5.3 EXPANSION OF CB-CD34* CELLS IS ACCOMPANIED BY MARGINAL
CHANGES OF GENE EXPRESSION BUT SIGNIFICANT ALTERATIONS OF GLOBAL
HISTONE MODIFICATION 33
5.4 REMODELLING OF H3K4ME
3
AND H3K27ME
3
MARKS UPON CULTURE OF
CB-CD34
+
CELLS 38
5.5 CLONOGENIC POTENTIAL OF EZH2 INHIBITOR-TREATED CB-CD34
+
CELLS
53
5.6 EZH2 INHIBITION INCREASES THE ENGRAFTING POTENTIAL OF EXPANDED
CB-CD34
+
CELLS 55
6 DISCUSSION 58
6.1 STFIA COCKTAIL MAINTAINS THE ENGRAFTING POTENTIAL OF CB-CD34
+
CELLS 58
6.2 GLOBAL LEVELS OF H3K4ME
3
AND H3K27ME
3
CHANGE UPON
EXPANSION OF CB-CD34
+
CELLS 61
6.3 EX VIVO EXPANSION OF CB-CD34
+
CELLS REMODELS THE DISTRIBUTION
OF H3K4ME
3
AND H3K27ME
3
HISTONE MODIFICATION MARKS 62
TABLE OF CONTENTS
6.4 THE TREATMENT OF STF-CULTURED CB-CD34
+
CELLS WITH TWO
DIFFERENT EZH2 INHIBITORS INCREASES HEMATOPOIETIC ENGRAFTMENT...66
7 MATERIALS AND METHODS 69
7.1 MATERIALS 69
7.1.1 CELL CULTURE MEDIA AND SUPPLEMENTS 69
7.1.2 ANTIBODIES 70
7.1.3 PRIMERS 71
7.1.4 KITS AND REAGENTS 72
7.1.5 CONSUMABLES 73
7.1.6 BUFFERS AND SOLUTIONS 73
7.1.7 ANIMALS 75
7.1.8 EQUIPMENT 76
7.1.9 SOFTWARES 76
7.2 METHODS 77
7.2.1 INFORMED CONSENT AND CB COLLECTION 77
7.2.2 CRITERIA FOR THE STORAGE OF SAMPLES PRIOR TO PROCESSING 77
7.2.3 ISOLATION OF CD34
+
CELLS FROM CB 77
7.2.4 CULTURE OF CD34
+
CELLS 78
7.2.5 IMMUNOSTAININGS OF FRESH AND CULTURED CD34
+
CELLS 79
7.2.6 INHIBITOR TREATMENT....? 79
7.2.7 COLONY-FORMING UNIT (CFU) ASSAYS 79
7.2.8 HEMATOXYLIN & EOSIN STAINING 80
7.2.9 FLOW CYTOMETRY MEMBRANE STAINING 81
7.2.10 INTRANUCLEAR STAINING 81
7.2.11 FACS
DATA ANALYSIS 82
7.2.12 RNA ISOLATION 82
7.2.13 DNASE TREATMENT AND CDNA SYNTHESIS 83
7.2.14 PRIMER DESIGN AND QUANTITATIVE REALTIME PCR 83
7.2.15 GLOBAL GENE EXPRESSION ANALYSIS (MICROARRAY) 84
7.2.16 WESTERN BLOT 85
7.2.17 CHROMATIN IMMUNOPRECIPITATION (CHIP) LOW CELL NUMBER 85
7.2.19 NSG MOUSE LINE 88
7.2.20 PRIMARY AND SECONDARY NSG TRANSPLANTATION 88
7.2.21 ORGANS PREPARATION AND ANALYSIS OF HUMAN CELL ENGRAFTMENT 89
7.2.22 STATISTICAL ANALYSIS 90
8 BIBLIOGRAPHY 91
9 ACKNOWLEDGMENTS 105
10 AFFIDAVIT 106
11 LIST OF PUBLICATIONS 108
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| spelling | Varagnolo, Linda Verfasser (DE-588)106833357X aut PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells von Linda Varagnolo Die Inhibition des PRC2 wirkt dem Kultur-bedingten Verlust des Repopulationspotenzials in humanen hämatopoetischen Stammzellen/Vorläuferzellen aus Nabelschnurblut entgegen 2014 108 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Online erschienen 2015 Würzburg, Univ., Diss., 2014 Hämatopoese (DE-588)4113823-5 gnd rswk-swf Epigenetik (DE-588)7566079-9 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Epigenetik (DE-588)7566079-9 s Hämatopoese (DE-588)4113823-5 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:20-opus-108073 https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-108073 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027840236&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Varagnolo, Linda PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells Hämatopoese (DE-588)4113823-5 gnd Epigenetik (DE-588)7566079-9 gnd |
| subject_GND | (DE-588)4113823-5 (DE-588)7566079-9 (DE-588)4113937-9 |
| title | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells |
| title_alt | Die Inhibition des PRC2 wirkt dem Kultur-bedingten Verlust des Repopulationspotenzials in humanen hämatopoetischen Stammzellen/Vorläuferzellen aus Nabelschnurblut entgegen |
| title_auth | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells |
| title_exact_search | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells |
| title_full | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells von Linda Varagnolo |
| title_fullStr | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells von Linda Varagnolo |
| title_full_unstemmed | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells von Linda Varagnolo |
| title_short | PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem/progenitor cells |
| title_sort | prc2 inhibition counteracts the culture associated loss of engraftment potential of human cord blood derived hematopoietic stem progenitor cells |
| topic | Hämatopoese (DE-588)4113823-5 gnd Epigenetik (DE-588)7566079-9 gnd |
| topic_facet | Hämatopoese Epigenetik Hochschulschrift |
| url | https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-108073 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027840236&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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