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Mammary Gland Stem Cells Development and Regeneration. Jayanti Tokas 1 , Puneet Tokas 2 , Rubina Begum 1 , Shailini Jain 3 and Hariom Yadav 3 1 Department of Biotechnology, JMIT, Radaur, Haryana, India 2 KITM, Kurukshetra, Haryana, India - PowerPoint PPT Presentation
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Mammary Gland Stem Mammary Gland Stem Cells Development and Cells Development and
RegenerationRegeneration
Jayanti Tokas1, Puneet Tokas2, Rubina Begum1, Shailini Jain3 and Hariom Yadav3
1Department of Biotechnology, JMIT, Radaur, Haryana, India2KITM, Kurukshetra, Haryana, India
3NIDDK, National Institute of Health, Bethesda, MD 20892, USAEmail: [email protected]
Mammary GlandMammary Gland
Secretory tissue Ductular system Connective
tissue
Ductular SystemDuctular System Starts at the alveoli & ends at the teat Starts at the alveoli & ends at the teat
canalcanalDuctule
Mammary duct
Gland cistern
Teat cistern
Streak canal
The Secretory TissueThe Secretory Tissue
Role of stem cells in Role of stem cells in Mammary glandMammary gland
• Mammary gland regeneration during• Pregnancy• Lactation• Involution
• MG stem cells control growth and development through self-renewal by
• Symmetric cell division • Asymmetric cell division
Symmetric cell division Asymmetric cell division
Tissue Growth
Possible lineages of mammary Possible lineages of mammary stem cellsstem cells
PluripotentPluripotent ProgenitorProgenitor
Lobule-limitedLobule-limited
Ductal-limitedDuctal-limited
Fully competentFully competent
Secretory lobules
Mammary ducts
Entire mammary epithelium
Self-renewing MultipotentSelf-renewing Multipotent
PluripotePluripotentnt ProgenitoProgenitorr
Fully competentFully competent
Lobule-limitedLobule-limited
Ductal-limitedDuctal-limited
Possible lineages of mammary Possible lineages of mammary stem cellsstem cells
Secretory lobules
Mammary ducts
Mammary Stem Cells Mammary Stem Cells (MaSCs)(MaSCs)
• Pale/light-staining cells
• Located throughout the mature MG
• ULLC are located between the basal and luminal layer of the MG with large nuclei.
• SLC - located in the basal layer
• Large dark cells (LDC) differentiated luminal cells
Mammary Gland Mammary Gland DevelopmentDevelopment
Birth to Puberty– Gland remains rudimentary– Relatively growth quiescent
Puberty• MG undergoes rapid growth and differentiation
at the tip of the terminal end buds (TEB) • TEB is surrounded by Cap cell layer that may
enter myoepithelial or luminal epithelial lineage
• Cap cells are thought to be multipotent stem cells
• TEBs are temporary niche - disappear as the duct reaches the end of the fat pad
Organization of duct and end bud
Nat Rev Cancer, 2004
MG development during MG development during pregnancypregnancy
• Growth is controlled by estrogen and progesterone
• Ductule-lobular growth- first 1/2 of gestation• Lobule-alveolar growth- second 1/2 gestation
Ductal
Lobuloalveolar gland
Lobulo-alveolar progenitor cells
Alveolar buds
Alveoli
MG development during MG development during Pregnancy & LactationPregnancy & Lactation
Mid pregnancy
Alveolar epithelium (I-transition of lactogenesis)
Milk proteins (secretion inhibited)
Parturition Milk (II-transition of lactogenesis)
Cells differentiate rapidly & continues till peak lactation
InvolutionInvolution
Degeneration of the secretory cells
Milking stopped Intramammary pressure Luminal pressure > blood pressure Milk biosynthesis ceases Alveoli degenerate first furthest from
the gland cistern Adipose cells occupy the empty space Lastly the duct system remains
MG development and involutionMG development and involution
Mammary stem cellsMammary stem cells
• Different mammary subpopulation havebon their cell surface CD24+ (heat-stable antigen), CD29hi (β1-integrin), CD49hif (α 6-integrin), Sca-1, etc
• MaSCs express low level of stem cell antigen (Sca-1)
• A single cell from the CD29hi/CD24+ or CD49hif CD24+ population was found to reconstitute a functional mammary gland