Cell renewal and regeneration

3 types of tissue regeneration

• permanent cells

• slowly regenerating cells

• regularly regenerating tissues

Permanent cells

• no regeneration once mature, rely on maintenance of existing cells

• non-dividing, long lived, cannot be replaced

  • ex. neurons (brain), photoreceptors (retina), auditory hair cells

slowly regenerating tissues

• mature differentiated cells divide to replace lost cells

• low turnover, can proliferate after injury

  • ex. liver (hepatocytes), pancreas (B-cells)

Regularly regenerating tissues

• continuous replacement from tissue-resident stem cells

• high turnover, requires stem cell niches

  • ex. skin, gut epithelium, blood

Stem cell definition

cells capable of self-renewal and differentiation into specialized types

Types of stem cells

• Totipotent

• Pluripotent

• multipotent

Totipotent stem cells

• all cell types including embryonic and extraembryonic

• forms entire organism

  • ex. zygote

Pluripotent stem cells

• all body cell types except extraembryonic

• forms tissues of all germ layers

  • ex. embryonic stem cells

Multipotent stem cells

• limited range within one lineage

• form several related cell types

  • ex. Hematopoietic stem cells

Transit amplifying cells

• integer progenitor cells derived from stem cells

• rapidly divide to expand cell number before differentiating

• maintain tissue homeostasis by protecting stem cells from exhaustion

• restricted to a specific lineage but can generate multiple mature cell types

  • ex. intestinal crypt cells that divide before forming absorptive or secretory cells

Stem cell niche

a specialized microenvironment that mainrains and regulates stem cells

• provides physical support and local signals (Wnt, Notch)

• keeps stem cells quiescent or activates them as needed

• limits number of stem cells

• prevents premature differentiation

  • ex. paneth cells in entestinal crypts supports Lgr5+ stem cells via Wnt signaling

  • ex. Bone marrow stromal cells support hematopoietic stem cells (HSCs)

Key signaling pathways

• Wnt: maintains stem cell state and promotes proliferation

• Notch: drives cell fate decisions and differentiation in the gut

• Apc gene: regulates Wnt signaling to prevent overgrowth

Asymmetric Division

produces one stem cell and one differentiated progenitor

symmetric Division

expands the stem cell pool during injury or stress

Quiescence

dormant state preventing stem cell exhuastion and mutation

Hematopoietic stem cells (HSCs)

• generate all blood lineages

• located in the bone marrow

• controlled by growth factors (erythropoietin, G-CSF) and niche interactions

Induced Pluripotent Stem Cells (iPSCs)

• reprogram somatic cells to a pluripotent state

• created by introducing transcription factors (Oct4, Sox2, Klf4, Myc)

• useful for research and regenerative medicine