Mammary Gland Stem Cells Development and Regeneration

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: yadavhariom@gmail.com

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