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04/04/16
STEMCELLS
Symmetriccelldivision
Atthebeginningofembryonic
development,stemcellsundergo
symmetriccelldivision.
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1
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Asymmetriccelldivision
1.  Self-renews
2.  DifferenBates
Thenatblastocyst
forma:onand
gastrula:onthe
stemcellsstartto
Progenitor cell
divide
asymmetrically
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Stem cell
Stem cell
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Whatisastemcell?
Stem cell
SELF-RENEWAL
(copying)
Identical stem cells
Stem cell
DIFFERENTIATION
(specializing)
Specialized cells
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(Embryonicstemcells)EScellshavetwoimportantproperBes.Thefistoneistheirnearlyinfiniteprolifera:on.Wecan
expandthenumbersofEScellsasmuchaswewant.Theotherimportantpropertyispluripotency,theabilityto
differenBateintonearlyalltypesofsomaBccellsthatexistinbody,suchasmusclecellsandnervecells.WefoundthatNAT1
isindispensableforthepluripotencyofmouseEScells.WhenwedisruptedtheNAT1funcBon,EScellsbecameunableto
differenBte.Becauseofthisunexpectedresult,myresearchinterestshiQedfromcancertostemcells.ShinyaYamanaka
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Whyself-renewANDdifferen:ate?
1stemcell
1stemcell
Selfrenewal-maintains
thestemcellpool
4specializedcells
Differen:a:on-replacesdeadordamaged
cellsthroughoutyourlife
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Stemcelljargon
Potency Pluripotent
Ameasureofhowmanytypesofspecializedcellastemcell
canmake
Canmakealltypesofspecializedcellsinthebody Embryonicstemcellsarepluripotent
Mul:potent Canmakemul:pletypesofspecializedcells,butnotalltypes
Tissuestemcellsaremul:potent
Typesofstemcell:
1)Embryonicstemcells
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Embryonic stem (ES) cells:
Challenges
u
grow
di
con
nder
grow under cond
embryonicstemcells
grow
u
gro
w
itions B
nder
cond
i
un
de
?
skin
A
Bons
rc
on
Bons
C
neurons
blood
dit
ion
sD
liver
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Types of stem cell:
2) Tissue stem cells
Tissue stem cells:
Where we find them
surfaceoftheeye
skin
tesBcles
muscles
brain
breast
intesBnes(gut)
bonemarrow
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Tissue stem cells:
What they can do
bloodstemcell
differenBaBon
foundin
bonemarrow
MULTIPOTENT
onlyspecializedtypesofbloodcell:
redbloodcells,whitebloodcells,
platelets
Types of stem cell:
3)Induced pluripotent (iPS)
stem cells
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ShinyaYamanaka
DepartmentofStemCellBiology,
InsBtuteforFronBerMedical
Sciences,KyotoUniversity,Kyoto
606-8507,Japan
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ShinyaYamanaka
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Inducedpluripotentstemcells(iPScells)
geneBcreprogramming =addcertaingenestothecell
cellfromthebody
inducedpluripotentstem(iPS)cell
behaveslikeanembryonicstemcell
differenBaBon
cultureiPScellsinthelab
Advantage:noneedforembryos!
allpossibletypesof
specializedcells
Adult(:ssue)stemcellsareuseful
in:ssueandorganregenera:on:
•Blood-formingstemcellstoregenerate
bloodandimmunesystems.
•Brain-formingstemcellstoregenerate
neuroprotecBvepotenBalinbrain.
•Skin-formingstemcells/burns.
•Skeletalmusclestemcellsformuscular
dystrophies.
•Mesenchymalcellculturesmakescar,fat,
boneandcarBlage;notanyotherBssues.
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Tissue stem cells:
Haematopoietic stem cells (HSCs)
NKcell
Tcell
Bcell
dendriBccell
megakaryocyte platelets
HSC
erythrocytes
macrophage
neutrophil
bonemarrow
eosinophil
basophil
commiWedprogenitors
specializedcells
Cellinvolvedinosteogenesis
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Tissue stem cells:
Mesenchymal stem cells (MSCs)
Bone(osteoblasts)
CarBlage(chondrocytes)
MSC
bonemarrow
Fat(adipocytes)
commiWedprogenitors
specializedcells
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Methodology for iPSCs generation
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Applications of iPSCs
DISEASE MODELING
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REGENERATIVE MEDICINE
InregeneraBvemedicinetheinjured
ordegeneratedBssuesarerepaired
bythegeneraBonofthoseBssues
withthehelpofiPSCsinlabsand
thentransplanBngthemtothesite
ofinjuryordegeneraBon.
REGENERATIVE MEDICINE
DifferentinjuriesasaresultofhumanacBviBes,
accidentsornaturalcalamiBescanalsobetreatedbythe
genetherapyuBlizingiPSCs.ThevariouscondiBonsthat
canbetreatedare:
Hematopoie:cdisorders,
Musculoskeletalinjury,
Spinalcordinjury,
liverdamagebythegenera:onofspecific
cellswiththehelpofiPSCs
(Liuetal.,2011b;Norietal.,2011;Tanetal.,2012;
Suzukietal.,2013).
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REGENERATIVE MEDICINE
Kazukietal.correctedthegeneBcdeficiency
iniPSCsfromahumanDuchheneMuscular
Dystrophy(DMD)pa:ent.TheyusedHuman
Ar:ficialChromosome(HAC)fortheexpressionof
completesequenceofDystrophin(DYS).Theyused
fibroblastsfromtheDMDpaBentforthegeneraBonof
iPSCs.HACwasusedforthecorrecBoninthedeleBon
ormutaBonintheDystrophingenepresentiniPSCs
bytransferofDYS-HAC(completegenomicsequence
ofdystrophininHAC)usingMicrocell-mediated
chromosometransfer(MMCT)(Kazukietal.,2009).
REGENERATIVE MEDICINE
Recently,thereareaccumulaBngdataon
theuseofiPSCforex-vivoblood
expansionofvariousblood
components.Theycanbeusedfor
thegenera:onofRedBloodCells
(RBCs)whichcouldbeuBlizedforthe
generaBonofbloodthatisrequiredover
theglobeforthepurposeoftreatmentof
variousdamagesordiseases.
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