Stam Cell Niche

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Transcript of Stam Cell Niche

Department of Hematology School of Medical

Sciences Tarbiat Modares

University

Najmaldin saki

Stem Cell Niche

: مسعود دکتر راهنما استادسلیمانی

الدین : نجم کننده ارائهساکی

HSCs

MSCs

CLP

CMP

GMP

MKEP

Cell fates available to a stem cell

Quiesce Differentiate

Self-renew Apoptose

Self-renewal or differentiation

Hematopoietic Stem Cell(HSC)

Hematopoietic Stem Cell(HSC)

Ratio in BM : 1̸$1̸0000 to 1̸$1̸00000

Characteristic:Sca-1̸Thy.1̸ LOW

Lin-(HLA-DR, CD71̸, CD45RA,CD38)

rTpo(C-MPL)CD1̸33+CD34+CD1̸1̸7+

Mobilizing:G-CSF or rh G-CSFM-CSFSCFIL3TpoMIP-1̸α

Stemness:Jagged-1̸N-Cadherin

Endothelial Cell

Clathrin-Coated pits

ED Cells:VWFCol IVLamVCAM1Selectin ECD34+CD14+CD45-SDF-1IL6

Ulex europeausAb CD34

CD22

Adventitial reticular cells

Characteristic:Alp +CD1̸0+CD1̸3+HLA IAlpha smoth-muscle actinVementinLamininFibronectinColl I,III,IVCD34-

receptor for:Nerve growth factor

Adipocytes

BM reticular cells ………..Adipocyte Starvation Saturated fatty acid

Express:LeptinOsteocalsinProlactin receptorVEGF

Maturin in vitro inhibited by:IL1̸ & IL1̸1̸

Stem cell erythroiedLeptin vs EPO

Fibroblasts

CD1̸4-

CD34-

CD45-

VCAM-1̸+

α-smooth muscle protien(ASP)α-smooth muscle actin(ASA)

Receptor for :bFGFPDGFEGF

TGFβ

Secret:GM-CSFM-CSFCSFIL6LIF

Secret:CollFibrinectinLamininProteogglycopro

Osteoblasts

Markers:CD34-STRO-1+RANKLSecret:TGFβB-FGFBMP-2M-CSFG-CSFGM-CSFIL1IL6ALPOstepontin(OPN)OsteocalcinCollfibronectinOPG

PTHWnt/βcatenin

osteoblastN-cad+

N-cad-Spindle shaped N-cadherin positive osteoblast

markers of primitive human marrow stromal cells and their more differentiated progeny

osteoclasts

CD34+STRO-1-TRAP+RANKCD51+CD54+CD68+

Secreat:MMPCatepsin K

M-CSF has a critical rol in Osteoclastojenesis

Osteopetrosis&

Osteoporosis

Vascular niche

Endosteal niche

M-CSF & RANKL & OPGIL7

Ost

HSC

HSC

مغز در رگ اندوتلیال نیچ) فعال) سلول استخوان

استئوبالست نیچمغز در

سلول) استخوانخاموش(

تمایزسلول بنیادی خونساز

ه رد یید

وئریت

ار

ه رد ست

الوب

ریکا

گام

یه

رد یید

وئیل

م

ه رد یید

وئفلن

O2

O2

غزم

یها

رگره

وادی

لیاتلدو

انی

هاول

سل

نوا

خست

ا

ObOs

CD1̸38

OPG

RANKL

RANK

MM

RANKL/OPG ratio

Enucleation of late-stage erythroblasts leads to the formation of two cells – a reticulocyte and a pyrenocyte

Pathways Involved in Stem CellSelf Renewal and Cancer

• Notch

• Hedgehog

• Bmi-1

• Wnt

Wnt

Extracellular space

CYTOPLASM

NUCLEUS

B-cateninB-catenin

B-catenin

GSK3

glycogen synthase kinase 3 APC

adenomatous polyposis coli

Axin

P

B-catenin

NUCLEUS

Extracellular space

CYTOPLASM

LRP

LRP

low-density lipoprotein receptor–related protein 5 and 6 (LRP5/6)

WntWnt inhibitory factor 1

frizzled-related protein

LRP

Kremen

SOSTDKK

Sclerostin(SOST gene product)

Dickkopf (Dkk) families

Interaction of the Dkk/LRP complex with kremen internalizesthe complex for degradation, thus diminishing the number

of Wnt coreceptors available for signaling

LRP

Wnt

GSK3

APC

Axin

Frat-1

Dsh

B-cateninB-catenin

B-cateninB-catenin

B-catenin

B-catenin

silencing mediator of retinoid and thyroid receptors and nuclear receptor corepressor

T cell factor/lymphoid enhancer binding factor

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