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Mammary Gland Stem Cells Development and Regeneration

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

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Mammary Gland Stem Cells Development and Regeneration

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  1. Mammary Gland Stem Cells Development and Regeneration Jayanti Tokas1, Puneet Tokas2, Rubina Begum1, Shailini Jain3 and Hariom Yadav3 1Department of Biotechnology, JMIT, Radaur, Haryana, India 2KITM, Kurukshetra, Haryana, India 3NIDDK, National Institute of Health, Bethesda, MD 20892, USA Email: yadavhariom@gmail.com

  2. Mammary Gland • Secretory tissue • Ductular system • Connective tissue

  3. Ductular SystemStarts at the alveoli & ends at the teat canal Ductule Mammary duct Gland cistern Teat cistern Streak canal

  4. The Secretory Tissue

  5. Role of stem cells in Mammary 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

  6. Symmetric cell division Asymmetric cell division Tissue Growth

  7. Possible lineages of mammary stem cells Self-renewing Multipotent Secretory lobules Lobule-limited Mammary ducts Ductal-limited Pluripotent Progenitor Entire mammary epithelium Fully competent

  8. Possible lineages of mammary stem cells Secretory lobules Lobule-limited Pluripotent Progenitor Fully competent Mammary ducts Ductal-limited

  9. Mammary Stem Cells (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

  10. Mammary Gland Development 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

  11. Organization of duct and end bud Nat Rev Cancer, 2004

  12. MG development during pregnancy • 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

  13. MG development during Pregnancy & 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

  14. Involution 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

  15. MG development and involution

  16. Mammary 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

  17. THANKS

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