Stem Cell Proliferation and Differentiation

Copyright
Contributors
Preface
Chromatin regulation and dynamics
Long noncoding RNAs and RNA-binding proteins
Distinct modes of pluripotency
Differentiation of pluripotent stem cells
Metabolic control of cell state
Conclusions and perspectives
Chromatin regulation and dynamics in stem cells
Chromatin compaction, structure, and function
Nucleosomes are formed from DNA interacting with an octamer of four histone proteins
Chromatin structure balances DNA compaction and accessibility
Chromatin dynamics regulate gene expression
ATP-dependent nucleosome remodeling complexes establish and maintain chromatin state
SWI/SNF family nucleosome remodeling factors
INO80 family nucleosome remodeling factors
ISWI family nucleosome remodeling factors
CHD family nucleosome remodeling factors
Summary
Histone modifications provide an additional layer of gene regulation
Histone acetylation and deacetylation
Histone methylation and demethylation
Polycomb group proteins mediate H3K27me3 and silencing of developmental genes
Histone chaperones and histone variants regulate chromatin structure
Histone H2A variants
H2A.Z is a histone variant associated with active transcription
H2A.X is a marker of DNA double-strand breaks
macroH2A is associated with repression and heterochromatin
Histone H3 variants
H3.3 marks regulatory, repetitive, and actively transcribed regions
CENP-A is a centromere-specific variant of histone H3
Histone chaperones
FACT facilitates H2A/H2B dimer exchange to promote nucleosome-templated activities
CAF1 and ASF1 promote incorporation of H3 and H4 onto newly synthesized DNA
HIRA deposits H3.3 at actively transcribed and regulatory regions of chromatin
ATRX/DAXX deposit H3.3 at telomeres and pericentric heterochromatin
The NAP1 family import newly translated histones from the cytoplasm to the nucleus
INO80 family members possess both nucleosome remodeling and histone chaperone activities
Chromatin structure is dynamic and highly regulated
Stem cell chromatin is dynamic and tuned to regulate cell fate
ES cells carefully regulate their chromatin via specialized transcription factors
Master regulators of pluripotency
Pioneer transcription factors
Embryonic stem cell chromatin is poised for action
Histone modifications are specifically regulated in stem cells to maintain pluripotency and facilitate differentiation
H3K56ac regulates pluripotency factors and developmental regulators
Bivalent promoters mark lowly expressed but poised genes in ES cells
Chromatin state is precisely regulated by nucleosome remodeling factors in ES cells
esBAF maintains stem cell pluripotency by preserving chromatin state
CHD proteins are regulators of ES cell pluripotency
MBD3/NuRD generally represses expression of differentiation genes
The ISWI remodeler ATPase SNF2H is essential during development
INO80 remodelers repress transcription of differentiation-associated genes
Polycomb group proteins silence developmental genes in ES cells
Variants of H2A and H3 have specialized roles in pluripotent cells
Long-range chromatin interactions are critical for regulation of pluripotency
ES cells regulate chromatin by common processes to preserve pluripotency
Acknowledgments
References
Role of lncRNAs in stem cell maintenance and differentiation
Introduction
Origin of noncoding RNAs
Core regulatory circuit in ESCs
LncRNAs: New determinants of ES cell fate
Long noncoding RNAs (lncRNAs) and their biological function
Discovery of lncRNAs: From sequences to function
Long noncoding RNAs and epigenetic regulation
Dissecting functional lncRNAs from transcriptional noise
LncRNAs in ESC pluripotency and somatic cell reprogramming
LncRNAs play a role in the differentiation of pluripotent stem cells
LncRNAs regulating the epigenome
The role of lncRNAs in dosage composition
LncRNAs implicated in imprinting developmentally associated genes
LncRNAs regulating signaling pathways in ESCs
LncRNAs regulating organ development
LncRNAs affecting neural development
LncRNAs regulating organogenesis
Cellular localization and maturation of lncRNAs
LncRNAs regulating the stability and functions of other RNAs
LncRNAs functioning in protein modification pathways
Mechanisms of lncRNA:DNA/RNA interaction
Allosteric regulation of proteins by lncRNAs
Single cell analysis of lncRNA functions
LncRNAs in disease progression
LncRNA knockouts often show lack of phenotype: The importance of context and redundancy
Conclusions
References
Further reading
Regulation of pluripotency and reprogramming by RNA binding proteins
Pluripotency and reprogramming
RNA binding proteins
Epigenetic regulation
RNA modification
Alternative splicing
Alternative polyadenylation
Nuclear retention and export of RNAs
Translation
mRNA stability and degradation
RNA helicases and DEAD-box helicase family
DDX3
DDX5/DDX17
DDX6
DDX18
DDX21
DDX47 and DDX52
Conclusions
Acknowledgments
References
Generating primed pluripotent epiblast stem cells: A methodology chapter
Introduction
Materials
Mouse embryonic fibroblasts (MEFs)
MEF isolation
Cryopreserving non-irradiated MEFs
Irradiating of MEFs
Cryopreserving irradiated MEFs
Thawing and culturing irradiated MEFs
Mouse embryonic stem cells (mESCs)
Derivation of mESCs
E3.5 blastocysts isolation
Culturing ESCs
Cryopreserving ESCs
Thawing of ESCs
Characterization of ESCs
Mouse epiblast stem cells (EpiSCs)
Derivation of EpiSCs from preimplantation embryos
Epiblast isolation and plating
EpiSC culture
Cryopreserving EpiSCs
Thawing of EpiSCs
EpiSC characterization
Epiblast like stem cells (EpiLCs)
Culturing ESCs
Differentiating ESCs into EpiLCs
Characterization of EpiLCs
Cryopreservation of EpiLCs
Equipment
Methods
Mouse embryonic fibroblasts (MEFs)
MEF isolation
Cryopreserving MEFs
Irradiating and cryopreserving MEFs
Preparation of MEF feeder tissue culture dishes
Mouse embryonic stem cells (mESCs)
Derivation of ESCs
Preparation of MEF feeder plates
Collecting mouse embryonic (E)3.5 mouse embryos
Plating and early culture
Disaggregation of blastocysts outgrowth
Passaging ESCs
Culturing ESCs
Cryopreserving ESCs
Thawing of ESCs
Characterization of ESCs
Morphological and molecular characterization of ESCs
IF-based detection of marker proteins in individual ESCs
Mouse epiblast stem cells (mEpiSCs)
Derivation of EpiSCs from E3.5 preimplantation embryos
Preparation of MEF feeder plates
Collecting E3.5 blastocysts
Plating and early culture
Disaggregation of blastocysts outgrowth
Culturing EpiSCs
Cryopreservation of EpiSCs
Thawing of EpiSCs
Characterization of EpiSCs
Morphological and molecular characterization of EpiSCs
IF-based detection of marker proteins in individual EpiSCs
EpiLCs
Generating EpiLCs from ESC
Preparation of gelatin-coated tissue culture dishes
Preparation of fibronectin-coated tissue culture dishes
Differentiating ESCs into EpiLCs
Cryopreserving EpiLCs
Thawing cells for EpiLC generation
Characterization of EpiLCs
Morphological and molecular characterization of EpiLCs
IF-based detection of marker proteins in individual EpiLCs
Discussion
Recipes
Notes
Acknowledgments
References
Differentiation of human pluripotent stem cells toward pharyngeal endoderm derivatives: Current status and ...
Introduction
Overview of the pharyngeal apparatus formation within the gut tube
Pharyngeal endoderm development and lineage specification within the pharyngeal pouches
Pharynx derivative pluripotent stem cell differentiation protocols: Current status
Parathyroid
Thyroid
Thymus
Applications of hPSCs for studying pharyngeal endoderm development and disease
Future directions for hPSC differentiation approaches toward pharyngeal derivatives
Reprogramming hPSCs toward pharyngeal derivatives
Single cell-omics for informing and assessing hPSC differentiation
Concluding remarks
Acknowledgments
References
Epigenetic metabolites license stem cell states
Introduction
Stem cell energetics
Metabolism of quiescent stem cells
Adult stem cells
Satellite cell metabolic switch during activation
Hematopoietic stem cell metabolism
Hair follicle stem cell
Pluripotent stem cell quiescence, diapause
Metabolism of active stem cells
Metabolism after fertilization
Metabolism of pre-implantation and post-implantation pluripotent stem cells
Metabolism of actively cycling adult stem cells: MSC as case-study
HIF, the master regulator of metabolism
Epigenetic signatures and epigenetic metabolites
Epigenetic signatures of naïve and primed pluripotent stem cells
Epigenetic signatures of adult stem cells
Epigenetic metabolites
Conclusion
Acknowledgments
References
Further reading