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CD34 a CD marker displayed on the surface of stem cells.

KIT a family of genes encoding plasma membrane class III receptor


tyrosine kinases. The viral gene, v-kit, is the oncogene of the
HardyZuckerman 4 strain of acutely transforming feline sarcoma
virus. The product of the protooncogene c-kit has five immunoglobulin-
like loops in the extracellular domain; the cytoplasmic
region contains a tyrosine kinase domain with an insert region,
and is myristoylated. Interaction with its ligand, steel factor (see
stem cell factor), brings about dimerization, leading to enhanced autophosphorylation
and binding of phosphatidylinositol 3-kinase
and phospholipase Cc. Kit and its ligand are highly expressed in
small-cell lung cancer and a significant proportion of testicular
germ cell tumours.

leukemia inhibitory factor abbr.: LIF; also called differentiatingstimulating


factor or differentiation-inducing factor; a cytokine produced
by fibroblasts, T cells, and macrophages. It is a monomer of
179 amino acids that maintains the pluripotent phenotype of embryonic
stem cells, and potentiates interleukin-3-dependent proliferation
of hemopoietic progenitors.

Today, genetic modifi cation


of the murine genome by ES cell technology is a seminal approach to understanding the
function of mammalian genes in vivo. ES cells have been reported for other mammalian
species (i.e., hamster, rat, mink, pig, and cow), however, only murine ES cells have
successfully transmitted the ES cell genome through the germline. Recently, interest
in stem cell technology has intensifi ed with the reporting of the isolation of primate
and human ES cells (811).
ES cells are isolated from the inner cell mass (ICM) of the blastocyst stage embryo
and, if maintained in optimal conditions, will continue to grow indefi nitely in an
undifferentiated diploid state. ES cells are sensitive to pH changes, overcrowding, and
temperature changes, making it imperative to care for these cells daily. ES cells that are
not cared for properly will spontaneously differentiate, even in the presence of feeder
layers and leukemia inhibitory factor (LIF). In addition, healthy cells growing in log
phase are critical for optimal transformation effi ciency in gene targeting experiments.
Targeted murine ES cells have little value if they lose the ability to transmit the
introduced mutations through the germline of the resulting chimeras. Therefore, it is
critical that murine ES cells have a normal 40 XY karyotype. It is standard practice in
our laboratory to have complete karyotypic analysis of all targeted ES cells prior to the
production of chimeras. The criteria used in our laboratory to qualify an ES cell clone
for making chimeras is that at least 50% of the chromosome spreads analyzed must be
40 XY. In our experience, our DBA/1LacJ ES cells (12) m
Feeder layerCells used in co-culture to maintain
pluripotent stem cells. For human embryonic stem
cell culture, typical feeder layers include mouse
embryonic fibroblasts (MEFs) or human embryonic
fibroblasts that have been treated to prevent
them from dividing.

Embryoid bodiesRounded collections of cells


that arise when embryonic stem cells are cultured
in suspension. Embryoid bodies contain cell types
derived from all three germ layers.

Blastema: A group of cells resembling stem cells in


function and instrumental in tissue or organ regeneration.
Hsp60 is required for regeneration of animal
organs from blastema. Mutation in Hsp60 leads into
mitochondrial defects and apoptosis

Clonote: The product of nuclear transplantation when


an enucleated egg is combined with an isolated
nucleus from a somatic cell. The term is coined from
the analogy of a zygote that is the product of the
natural fertilization of an egg by a sperm. Production
of a clonote would be, in all essential ways,
reproductive cloning. A clonote could also be
exploited for stem cell research but it appears
inadvisable to use it for human reproduction on both
ethical and biological grounds.

MAPCS (multipotent adult progenitor cells): These are


universal stem cells present in small numbers in
some adult tissues and have the capacity to produce
other types of cells in a manner similar to embryonic
stem cells.

Mouse (Mus musculus, 2n = 40): Rodent belonging


to the subfamily Murinae, including about 300 species
of mice and rats (see Fig. M122). They are
extensively used in genetics and physiological studies
because of their small size (2540 g), short lifecycle
(10 weeks), life span of about two years, gestation
~19 days, having 510 pups/litter, and their practically
continuous breeding. The genome is ~1.8 10 6
kDa in 2n = 40 chromosomes. The mouse genome is
~14% smaller than the human genome, yet about 40%
of their genomes can be aligned. In one m2 laboratory
space up to 3,000 individuals can be studied annually.
From embryonic stem cells, viable, fertile adults can
be differentiated (Eggan K, Jaenisch R 2003 Methods
Enzymol 365:25). Very detailed linkage information
is available. According to the 1996 map the genetic
length, based on 7,377 genetic markers including
RFLP and other markers, is 1,360.9 units. The
average spacing between markers then was 400 kb.
A nucleotide sequence draft became available in
2002 and the final annotated sequence was expected
by 2006. Transformation, gene targeting and other
modern techniques of molecular genetic manipulations
ar

NANOG: A human chromosome 12p region encoded


homeodomain protein directing the infinite propagation,
and sustaining pluripotency, in embryonic stem
cells. The mouse homolog is quite similar. Primarily
in human cells, the C-terminus domain is involved in
gene transactivation whereas in mice the N-terminal
is more active
Niche: A sheltered environment that sequesters stem
cells from stimuli to differentiate. The niche(s) is/are
involved in transdetermination and self-renewal
of the stem cells. The niche is not necessarily a
topological concept because the hematopoietic cells
are circulatory; thus, the niche has physiological
determinants too. Several different paracrine signals,
metabolic, physical and neural factors contribute
to the definition of the niche. The Jak-Stat signaling
pathway mediates in Drosophila spermatogenesis
from stem cells.

Oct: This is a mammalian gene regulatory protein (helixturn-


helix transcription factors) with octa recognition
sequence: ATTTGCAT. Oct-1 and Oct-2 regulate B
cell differentiation. Oct3/4 mediates differentiation
and dedifferentiation of embryonic stem cells. The
Oct-6 transcription factor regulates Schwann cell
differentiation. The presence of Oct-1 allele may lead
to a fourfold increase in susceptibility to the cerebral
form of malaria.

Pheresis (apheresis): The medical procedure of withdrawal


of blood; after fractionation, some fraction(s)
are reintroduced. Such a protocol may use stem cells,
transfect them with a vector or apply to them
chemotherapy, and eventually place them back in
the body of the same individual.

Phialide: Fungal stem cells from which conidia are


budded.

piRNA (Piwi interacting RNA): 26-31-nucleotide-long


RNA regulating germ and stem cell development
when bound to Argonaute family proteins (Aubergine,
Piwi, Ago3). In mouse, the MIWI/Piwi RNA
associates with the polysomes and chromatoid body
during spermatogenesis
Plasticity: In general, the ability of a cell or organism to
display different expressions (phenotype) dependent
on the environment. The ability of cells to change
from what they normally are enables them to perform
tasks not normally found in differentiated cells.

Pluripotency: A cell with pluripotency has the ability


to develop into various, but not necessarily all types
of tissues. Embryonic stem cells (from the inner
mass of blastocysts), embryonic germ cells (primordial
cells of the gonadal ridge), and the mesenchymal
stem cells of the bone marrow possess pluripotency.
Transcription factor Zfx controls the selfrenewal
of embryonic and hematopoietic stem cells
(Galan-Caridad JM et al 2007 Cell 129:345). The
good cultures may grow for more than 70 doublings
(270 1020) and may be free of chromosomal defects.
The ability of the embryonic stem cells to differentiate
into many types of cells is regulated by MYC and
Nanog proteins that regulate transcription factors,
signal molecules, and suppress lineage specific cells.
These two factors target a core set of 345 genes. The
mouse and human MYC and Nanog target sites
overlap in _9 to 13% (Loh Y-H et al 2006 Nat Genet
38:431). Nanog proteins enable the reprogramming of
somatic cells into pluripotent stem cells after fusion
with embryonic stem cells of mouse (Silva J et al 2006
Nature [Lond] 441:997). Histone3 arginine26 methylation
appears to be a crucial event in the formation of
the pluripotent inner cell mass of the four-cell stage
mouse embryos. CARM1 methyltransferase activity
also upregulates Nanog and Sox2 proteins