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核心提示:ContentsEmbryonic Stem Cell Markers Hematopoietic Stem Cell
Markers Mesenchymal/Stromal Stem Cell Markers Neu

Seminar Abstract:



  • Embryonic Stem Cell Markers
  • Hematopoietic Stem Cell Markers
  • Mesenchymal/Stromal Stem Cell Markers
  • Neural Stem Cell Markers
  • References

While stem cells are best defined functionally, a number of molecular
markers have been used to characterize various stem cell populations.

Although functions have yet to be ascertained for many of these early
markers, their unique expression pattern and timing provide a useful
tool for scientists to initially identify as well as isolate stem cells.
This mini-review summarizes evidence regarding the roles of specific
markers in defining embryonic, hematopoietic, mesenchymal/stromal, and
neural stem cell populations. For most of the molecules discussed,
studies performed both in vitro and in vivo support their significant
role in characterizing stem cells. Until more is known about the novel
marker-negative stem cell population, however, uncertainty still exists
regarding the benefits of using these markers alone or in various
combinations when identifying and isolating cells for stem cell

Recent advances in stem cell biology may make possible new approaches
for the treatment of a number of diseases. Such approaches could involve
cell replacement therapy and/or drug treatment to stimulate the body’s
own regenerative capabilities. Realizations of these approaches will
require identification of renewable cell sources of engraftable
functional cells, an improved ability to manipulate stem cell
proliferation and differentiation, as well as a better understanding of
the signaling pathways that control their fate. Cell-based phenotypic
and pathway-specific screens of synthetic chemical and arrayed
cDNA/siRNA libraries have recently provided a number of small molecules
and genes that can be used to selectively control stem cell fate. Such
compounds and genes will likely provide new insights into stem cell
biology, and may ultimately contribute to effective medicines for tissue
repair and regeneration


Embryonic Stem Cell Markers

Oct-4: Oct-4 , one of the POU transcription factors, was originally
identified as a DNA-binding protein that activates gene transcription
via a cis-element containing octamer motif.1 It is expressed in
totipotent embryonic stem and germ cells.2, 3 A critical level of Oct-4
expression is required to sustain stem cell self-renewal and
pluripotency.4 Differentiation of embryonic stem cells results in down-
regulation of Oct-4, an event essential for a proper and divergent
developmental program.5 Oct-4 is not only a master regulator of
pluripotency that controls lineage commitment, but is also the first and
most recognized marker used for the identification of totipotent ES

SSEAs : SSEAs were originally identified by three monoclonal antibodies
recognizing defined carbohydrate epitopes associated with lacto- and
globo-series glycolipids, SSEA-1, -3 and – 4.6 SSEA-1 is expressed on
the surface of preimplantation-stage murine embryos and has been found
on the surface of teratocarcinoma stem cells, but not on their
differentiated derivatives.7,8 The oviduct epithelium, endometrium and
epididymis, as well as some areas of the brain and kidney tubules in
adult mice have also been shown to be reactive with SSEA-1 Abs.9 SSEA-3
and -4 are synthesized during oogenesis and are present in the membranes
of oocytes, zygotes and early cleavage-stage embryos.10,11 Biological
roles of these carbohydrate-associated molecules have been suggested in
controlling cell surface interactions during development.6
Undifferentiated primate ES cells, human EC and ES cells express SSEA-3
and SSEA-4, but not SSEA-1. Undifferentiated mouse ES cells express
SSEA-1, but not SSEA-3 or SSEA-4.12,13


Hematopoietic Stem Cell Markers

CD34: The cell surface sialomucin CD34

has been a focus of interest ever since it was found expressed on a
small fraction of human bone marrow cells.14 The CD34+-enriched cell
population from marrow or mobilized peripheral blood appears responsible
for most of the hematopoietic activity.14 – 21 CD34 has therefore been
considered to be the most critical marker for hematopoietic stem cells .
CD34 expression on primitive cells is down-regulated as they
differentiate into mature cells.22 It is also found on clonogenic
progenitors, however, and some lineage-committed cells.23 Although its
precise function is still unknown, the pattern of expression of CD34
suggests that it plays a significant role in early hematopoiesis.22 The
theory of CD34 being the most primitive HSC marker, however, has
recently been challenged. Osawa et al. first demonstrated that murine
HSCs could be CD34 negative.24 In addition, a low level of engraftment
and hematopoietic capacity has been demonstrated in human CD34- cells.25
Transplantation studies also showed repopulating activity in a CD34-
cell population in fetal sheep.26 Additionally, studies have shown that
both murine and human CD34+ cells may be derived from CD34- cells.27,28
Collectively, these reports suggest the possibility that HSCs may be
CD34+ or CD34- and that selection of cells expressing CD34 might result
in exclusion of more primitive stem cells. Nevertheless, almost all
clinical and experimental protocols including ex vivo culture, gene
therapy, and HSC transplantation are currently designed for cell
populations enriched for CD34+ cells.

CD133: CD133, a 120 kDa, glycosylated protein containing five
transmembrane domains , was identified initially by the AC133 monoclonal
Ab, which recognizes a CD34+ subset of human HSCs.29,30 A CD133 isoform,
AC133-2, has been recently cloned and identified as the original surface
antigen recognized by the AC133 Ab.31 CD133 may provide an alternative
to CD34 for HSC selection and ex vivo expansion. A CD133+ enriched
subset can be expanded in a similar manner as a CD34+ enriched subset,
retaining its multilineage capacity.32 Recent studies have offered
evidence that CD133 expression is not limited to primitive blood cells,
but defines unique cell populations in non-hematopoietic tissues as
well. CD133+ progenitor cells from peripheral blood can be induced to
differentiate into endothelial cells in vitro.33 In addition, human
neural stem cells can be directly isolated by using an anti-CD133 Ab.34

ABCG2: ABCG2 is a determinant of the Hoechst-negative phenotype of side
population and found in a wide variety of stem cells, including
HSC.35,36 ABCG2 is a member of the family of ABC transporters and was
first identified in a breast cancer cell line.37 It belongs to the
half-transporter group and is unique as it is localized to the plasma
membrane .38 The expression of ABCG2 appears greatest on CD34- cells and
is down-regulated with the acquisition of CD34 on the cell surface.35
Down-regulation in ABCG2 expression is also observed in various
committed hematopoietic progenitors.39 ABCG2 may therefore serve as a
more promising marker than CD34 for primitive HSC isolation and
characterization. The expression pattern of ABCG2, however, is not
limited to HSC. ABCG2 expression exclusively characterizes the Hoechst
SP phenotype in cells from diverse sources, including monkey bone
marrow, mouse skeletal muscle and ES cells.35 The potential plasticity
of SP cells has been demonstrated by studies showing that cardiomyocytes
and muscle can be regenerated from transplanted bone marrow-derived SP
cells.40,41 Exclusive expression of ABCG2 on SP cells suggests that
ABCG2 may be a potential marker for positive selection of pluripotent
stem cells from various adult sources. ABCG2 has been implicated in
playing a functional role in developmental stem cell biology .

Sca-1: Sca-1 , an 18 kDa phosphatidylinositol-anchored protein, is a
member of the Ly-6 antigen family.43 Sca-1 is the most recognized HSC
marker in mice with both Ly-6 haplotypes as it is expressed on
multipotent HSCs.44,45 An anti-Sca-1 Ab is frequently used in
combination with negative selection for expression of a number of cell
surface markers characteristic of differentiated cells of hematolymphoid
lineages to identify and isolate murine HSCs. Sca-1+ HSCs can be found
in the adult bone marrow, fetal liver and mobilized peripheral blood and
spleen within the adult animal.44-49 Sca-1 has also been discovered in
several non-hematopoietic tissues,43 however, and can be used to enrich
progenitor cell populations other than HSCs.50 Sca-1 may be involved in
regulating both B and T cell activation.51-54


Mesenchymal/Stromal Stem Cell Markers

STRO-1: The murine IgM monoclonal Ab STRO-1, produced from an
immunization with a population of human CD34+ bone marrow cells, can
identify a cell surface antigen expressed by stromal elements in human
bone marrow.55 From bone marrow cells, the frequency of fibroblast
colony-forming cells is enriched approximately 100-fold in the
STRO-1+/Glycophorin A- population than in the STRO-1+/Glycophorin A+
population.55 A STRO-1+ enriched subset of marrow cells is capable of
differentiating into multiple mesenchymal lineages including
hematopoiesis-supportive stromal cells with a vascular smooth
muscle-like phenotype, adipocytes, osteoblasts and chondrocytes.56-59
STRO-1 is a valuable Ab for the identification, isolation and functional
characterization of human bone marrow stromal cell precursors, which are
quite distinct from those of primitive HSCs.

另外,还有这些marker: CD71, CD105, SH2. SH3, SH4


Neural Stem Cell Markers

Nestin: Nestin is a class VI intermediate filament protein.60,61
Although it is expressed predominantly in stem cells of the central
nervous system ,62 its expression is absent from nearly all mature CNS
cells.63 Nestin has been the most extensively used marker to identify
CNS stem cells within various areas of the developing nervous system and
in cultured cells in vitro.34,64-68 The role of nestin in CNS stem cell
biology, however, remains undefined. Although nestin does not form
intermediate filaments by itself in vitro a-internexin to form homo- and
heterodimer, coiled-coil complexes that may then form intermediate
filaments.69 Its transient expression has been suggested to be a major
step in the neural differentiation pathway.61 Nestin expression has also
been discovered in non-neural stem cell populations, such as pancreatic
islet progenitors70-72 as well as hematopoietic progenitors.73

PSA-NCAM : The regulated expression of neural cell adhesion molecule
isoforms in the brain is critical for many neural developmental
processes. The embryonic form of NCAM, PSA-NCAM, is highly
polysialylated and is mainly expressed in the developing nervous
system.74 PSA-NCAM may be related to synaptic rearrangement and
plasticity.75 In the adult, PSA-NCAM expression is restricted to regions
that retain plasticity.76 A neuronal-restricted precursor identified by
its high expression of PSA-NCAM can undergo self-renewal and
differentiate into multiple neuronal phenotypes.77 PSA-NCAM+ neonatal
brain precursors are restricted to a glial fate and thyroid hormone can
modulate them into an oligodendrocyte fate.78-80 Polysialic acid
modification significantly decreases NCAM adhesiveness and therefore, it
was originally suggested PSA-NCAM works as a purely anti-adhesive factor
that modulates cell-cell interactions in promoting brain plasticity.
Increasing evidence indicates that PSA-NCAM may interact with secreted
signaling molecules to perform an instructive role in development.81,82

p75 Neurotrophin R : p75 NTR, also named low affinity nerve growth
factor receptor, is a type I transmembrane protein that belongs to the
tumor necrosis factor receptor superfamily .83 It binds to NGF, BDNF,
NT-3 and NT-4 equally . p75NTR, when activated in the presence of Trk,
enhances responses to neurotrophin . TrkC receptors working together
with p75 NTR have been suggested to serve critical functions during the
development of the nervous system.85 Neural crest stem cells have been
isolated based on their surface expression of p75NTR.86,87 Freshly
isolated p75NTR+ NCSCs from peripheral nerve tissues can self-renew and
generate neurons and glia both in vitro and in vivo. In addition,
neuroepithelial-derived p75NTR+ cells are also able to differentiate
into neurons, smooth muscle and Schwann cells in culture.88 Recently,
p75 NTR has been used as a marker to identify mesenchymal precursors as
well as hepatic stellate cells.89,90



题目:Discovering Factor Combinations Deciding Cell Fate Using CRISPR
Activation Screening报告人:于晨博士,加州大学Gladstone研究所

题目:Nanomedicine: From Anti-Cancer to

题目:Molecular Mechanisms of LncRNA in the Self-renewal of Cancer Stem

Discovering Factor Combinations Deciding Cell Fate Using CRISPR
Activation Screening
内容摘要:Comprehensive identification of factors
that can specify neuronal fate could provide valuable insights into
lineage specification and reprogramming, but systematic interrogation of
tranion factors, and their interactions with each other, has proven
technically challenging. We developed a CRISPR activation approach to
systematically identify regulators of neuronal-fate specification. We
activated expression of all endogenous tranion factors via a pooled
CRISPRa screen in embryonic stem cells, revealing genes a number of
genes inducing neuronal fate. Systematic CRISPR-based activation of
factor pairs allowed us to generate a genetic interaction map for
neuronal differentiation, with confirmation of top individual and
combinatorial hits as bona fide inducers of neuronal fate. Several
factor pairs could directly reprogram fibroblasts into neurons, which
shared similar tranional programs with endogenous neurons. This study
provides an unbiased discovery approach for systematic identification of
genes that drive cell-fate
Stem Cell,Blood,Journal of Molecular Cell Biology, Cell Chemical
Nanomedicine: From Anti-Cancer to Anti-Bacteria
内容摘要:With the
development of nanotechnology, a variety of functionalized drug delivery
systems have started to show great potential for disease treatment.
Fully understanding of the interaction between nanodrug and living
system is the prerequisite for its clinical application. On one hand,
nanomedicine must be evaluated and tested in vitro/vivo before the
clinical use; on the other, fully understanding of their interacting
mechanism could contribute to design more effective nanodrugs. We have
explored the most important factors, e.g. size and surface chemistry, in
influencing nanodrug delivery, and conducted a systematic study to
understand the roles in anti-cancer and anti-bacteria applications.
Followed, according to these unique bio-effects, a novel multi-stage
drug delivery system was designed and fabricated to achieve better tumor
targeting and cancer therapy. Additionally, through mechanochemistry
study, the drug activity was successfully regulated, a further
controllable therapeutic effect was achieved as
Nanotechnology,PNAS,Cancer Research,ACS Nano,Advanced
Horizons期刊Community Board
Molecular Mechanisms of LncRNA in the Self-renewal of Cancer Stem
内容摘要:Long non-coding RNAs are recognized as a class of
genes, longer than 200 nucleotides trans lacking protein-coding
potential. Cancer stem cells refer to a subset of tumor cells with many
phenotypic and functional properties of normal stem cells, including the
ability of self-renewal and differentiation. In this lecture, we will
talk about molecular mechanisms of lncHDAC2 and lncGATA6 in cancer stem
cells. LncHDAC2 is highly expressed in liver CSCs and required for the
self-renewal maintenance of liver CSCs via recruiting the NuRD complex
onto the promoter of PTCH1 to inhibit its expression and activate
Hedgehog pathway. Highly expressed in colorectal CSCs, lncGata6 recruits
the NURF complex onto the Ehf promoter to induce its tranion, which
promotes the expression of Lgr4/5 to enhance Wnt signaling
activation,leading to self-renewal of intestinal CSCs. Our findings
suggest that lncRNAs may serve as biomarkers for the diagnosis and
potential drug targets for diverse tumors according to their functions
in self-renewal maintenance of CSCs. Targeting lncRNAs will be effective
in clinical applications in cancer
Nature Immunology,Nature Cell Biology,Journal of Hepatology
等国际权威杂志发表文章 11



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