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Glossary:
developmental potency: the degree to which primitive cells are capable of forming distinct types
of cells and tissues
differentiation: cellular development from a primitive stage towards a more mature cell
directed differentiation: forcing differentiation from a primitive to a more mature cell type via
genetic and/or environmental manipulation
disease modeling: the use of laboratory cell culture or animal research to obtain new
information about human disease or illness
drug screening: the use of cells and tissues in the laboratory to identify drugs with a specific
function
ectoderm: one of the three basic germ layers that includes nervous tissues and skin
embryonic stem (ES) cell: a cell derived from the inner cell mass of the pre-implantation
blastocyst (around 5-7 days post-fertilization in humans) that is pluripotent and capable of selfrenewal in cell culture
The cycle of developmental potency
M. William Lensch*
& Stephen Sullivan†
Development occurs along a continuum where cyclic potency rises and falls as life transitions through stages of highly-specialized cells (gametes) and multicellular, integrated organisms. This system may now be manipulated
via a series of genetic methodologies to direct differentiation as well as to reprogram cells to states bearing greater developmental plasticity. Each of these procedures functions in large part due to the principle of nuclear
equivalence which describes how the vast majority of cells in a multicellular organism each contain the same genetic material, yet make use of only subsets of gene expression in order to generate cells and tissues that are
functionally distinct from one another. Just as cellular reprogramming methodologies such as Nuclear Transfer have permitted a detailed, (though as yet incomplete), understanding of fate transitions between cells, new methods
to direct differentiation are rapidly being elucidated.
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endoderm: one of the three basic embryonic germ layers which includes gut tissues
epigenetic: literally "upon the genome". Chemical modifications of DNA that do not alter a gene's
sequence, but impact gene expression and may also be inherited. Epigenetic modifications to
DNA are very important to both imprinting and cellular reprogramming
epigenetic reprogramming: alteration of the pattern of gene expression in a cell via chemical
modifications that do not change a gene's sequence of base pairs
Fertilisation/IVF
Parthenotes
Cell Fusion
Germline
Nuclear Transfer
Tumors
iPS
Induced pluripotency (iPS) transduction
fertilization: the union of sperm and egg
functional assay: to test a cell's gene expression or developmental state by evaluating its growth
or ability to live under certain circumstances
gene expression: whether or not a gene is active ("on") or inactive ("off")
germ cell: eggs, sperm, and their progenitors (primordial germ cells or PGC)
induced pluripotent stem (iPS) cell: a type of pluripotent cell made directly from a somatic cell
infection: to expose target cells to a mixture of viral particles that contain new genetic material
one wishes to functionally evaluate
lentivirus: literally, "slow virus". A specific type of virus with an RNA genome (such as HIV) that
can be engineered to deliver and integrate new genetic material into target cells. Lentivirus has
certain advantages over other retroviruses including that it can deliver its genetic payload to the
nucleus of non-dividing target cells
mesoderm: one of the three basic embryonic germ layers which includes blood, muscle, and bone
multipotency: a degree of developmental versatility that is less than totipotent and pluripotent.
Multipotent means a stem cell may form many types of cells in a given lineage, but not cells of
other lineages. For example, a multipotent blood stem cell can form the many different types of
blood cells (red, white, platelets, etc...), but it cannot form neurons. Most adult or tissue-specific
stem cells are multipotent.
niche: the cellular microenvironment
nuclear reprogramming: essentially, this is mechanistically the same as epigenetic
reprogramming though it corresponds specifically to the use of nuclear transfer
nuclear transfer: also known as somatic cell nuclear transfer (SCNT), therapeutic cloning,
research cloning, or cellular cloning. The process of removing and discarding the nucleus which
contains the genetic material from one cell and replacing it with the intact nucleus of another
nullipotency: incapable of differentiation
oligopotency: a degree of differentiation that is less than multipotent and describes progenitor
cells capable of forming a small set of differentiated cell types
Extraembryonic Markers
Pluripotent SC Markers
CDX2: ab15258
FGFR2: ab10648
hCG: ab400
HAND1: ab11846
5T4: ab45520
Nanog: ab21603
Oct3/4: ab19857
SOX2: ab15830
SSEA1: ab16285
Tra-1-60: ab16288
Tra-1-81: ab16289
oncogene: a gene initially identified via its role in certain cancers. Oncogenes may cause or
contribute to cancer when abnormal though it is important to note that they are not always cancer
associated; they have normal functions in healthy cells
Viral infection of fibroblasts
pluripotency: a developmental potential that describes an ability to differentiate into all types of
specialized cell in the body. Scientifically, a cell is termed pluripotent if it is capable of making
derivatives of all three embryonic (basic) germ layers: endoderm (gut tissue), mesoderm
(including blood, muscle, and vessels), and ectoderm (such as skin and nerve)
progenitor cell: the primitive forbearer of a more mature cell
program: the gene expression profile (both what genes are expressed and when) that directs a
primitive cell to a specific, more mature type of cell
reprogramming: to drive differentiation "backwards" to a more primitive type of cell
retrovirus: A specific type of virus with an RNA genome that can be engineered to deliver and
integrate new genetic material into target cells
self-renewal: the process of a stem cell making more copies of itself (i.e. duplication)
somatic cell: a cell of the body not including germ cells
Adult stem cells
Cancer stem cells
Embryonic stem cells
Endothelial progenitors
Germline stem cells
Hematopoietic progenitors
Intracellular molecules
Lymphoid markers
Myeloid markers
Surface markers
Lineage markers
Mesenchymal stem cells
Neural stem cells
Wnt, TGFb signalling pathways
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parthenogenesis (parthenotes): literally, "virgin birth"; the activation of an unfertilized egg cell
to being dividing
plasticity: a cell's capacity to form different cell types
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Extraembryonic
Chorion
Amnion
Trophoblast
Villi
Allantois
stem cell: a general term describing a primitive type of cell capable of both unlimited selfrenewal and differentiation
totipotency: the degree of differentiation describing a capacity to make all of the cells in the
adult body as well as the extraembryonic tissues including the placenta. The fertilized egg
(zygote) is totipotent as are the early cleaved cells (blastomeres)
transcriptional profile: the state of gene expression in a given cell or tissue type
Pluripotent stem cells
Germ Cells Markers
Dppa4: ab31648
DDX4/MVH: ab13840
Fragilis: ab15592
PIWIL2: ab36764
Stella: ab19878
TBX2/EOMES: ab23345
Endoderm Markers
Gata4: ab61767
FoxA2: ab40874
PDX1: ab19379
Nodal: ab55676
Sox7: ab49163
Sox17: ab33101
Mesoderm Markers
Brachycury: ab20680
GSC: ab58352
LEF1: ab53293
MOX1: ab23279
Tie1: ab27851
Human Embryonic Stem Cells
The Practical Handbook
Sullivan, Cowan and Eggan (Editors)
Ectoderm Markers
Cripto1: ab19917
EN1: ab32857
GFAP: ab7620
Islet 1: ab22849
LIM1: ab14554
Nestin: ab27952
The first centralised collection of methods
used in human pluripotent stem cell biology.
Almost all of the protocols listed can be
used with both human induced pluripotent
and embryonic stem cells.
transduction: the use of viral particles to introduce new genetic material into a cell
From the reviews:
transfection: the use of chemical methods, most often lipid containing vesicles, to introduce new
genetic material into a cell
transformation: when a cell becomes functionally abnormal in the process of malignancy, often
obtaining a new capacity to multiply indefinitely or under new circumstances
transit amplifying cell: a stem cell-derived intermediate that is capable of extensively dividing
to make numerous downstream cell types. Importantly, this large degree of cellular multiplication
is both rapid and limited and thus, not the same as self-renewal
transplantation: to introduce new cells, tissues, or organs into a host (i.e. transplant recipient)
trophectoderm: the basic, extraembryonic layer of the early embryo
unipotency: capable of making only a single type of cell
zygote: the fertilized egg
Abbreviations
ES/hES: embryonic stem cell and human embryonic stem cell
iPS: induced pluripotent cell
IVF: in vitro fertilization
NT: nuclear transfer
SCNT: somatic cell nuclear transfer
Germ cells
Endoderm
Mesoderm
Ectoderm
Primordial germ
cells (PGC)
Oocytes
Sperm
Liver
Intestine
Lung
Pancreas
Cardiomyocytes
Endothelial cells
Osteogenic cells
Hematopoietic cells
Forebrain neurons
Dopaminergic neurons
Spinal motor neurons
Skin cells
Pluripotency can be artificially restored to human somatic cells by viral
transduction of genes coding for stem cell factors. This process only requires
SOX2 and OCT3/4 integration but the frequency of reprogramming is
significantly increased by co-infection with virus coding for KLF4 and c-MYC.
While iPS cells will currently be of assistance to disease modelling and drug
screening, random integration of genes presents an oncogenic risk and so
constitutes a significant obstacle to using iPS cells therapeutically. Current
efforts seek to remove the need for such vectors.
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REGENERATIVE MEDICINE
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DIFFERENTIATION
M. William Lensch is at the *Department of
Pediatrics, Harvard Medical School/Division of
Hematology, Children's Hospital Boston, One
Blackfan Circle, Boston, Massachusetts, 02115,
USA.
Stephen Sullivan is at the †Department of Molecular
and Cell Biology, Harvard University, 7 Divinity
Avenue, Cambridge, Massachusetts, 02138, USA
and the Regenerative Medicine Institute, National
University of Ireland, Galway, Ireland.
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