Tissue Maintenance Cell turnover by division/death –Division of fully differentiated cells –Division of stem cells Turnover components within cell

Turnover In Photoreceptor Cells Permanent cells; renewal of membrane discs and proteins Membrane proteins synthesized, placed in new discs at base Old discs at tip are phagocytosed

Division of Differentiated Cells Hepatocytes in liver; beta cells of pancreas Balance of cell division and cell death Endothelial cells during angiogenesis

Angiogenesis Division of differentiated endothelial cells Endothelial tip cells lead angiogenesis

Regulation of Angiogenesis Secreted by many cells in response to need for oxygen Stimulates endothelial cells VEGF is key regulator

Basal layer contains stem cells Some daughter cells commit to terminal differentiation Multiple steps in differentiation as cells move outward Cells In Epidermis

Can divide without limit Each daughter either remains as stem cell or commits to terminal differentiation Stem Cells

Limited divisions following commitment to terminal differentiation Regulation at multiple steps in response to conditions Differentiation Of Daughter Cells

Hemopoiesis From Multipotent Stem Cells Many cell types derived from common stem cell Terminal differentiation involves series of progressive restrictions Committed progenitor cells undergo limited division

Regulation By Colony- Stimulating Factors Act on particular hemopoietic cells Promote division, survival, and differentiation Erythropoietin targets erythrocyte colony forming cells Multiple CSFs act on common progenitor for neutrophils and macrophages

Stem Cell Engineering –Hemopoietic stem cells –Epidermal stem cells –Neural stem cells Stem cells from adult- restricted to forming specific cell types ES cells- pluripotent

Pluripotent cells can differentiate into any cell type given appropriate combination of signals Generate various progenitors in culture ES Cells

Sources of ES Cells Early embryo- not patient specific Personalized ES cells –Somatic cell nuclear transplantation –Induced pluripotent stem cells

Somatic Cell Nuclear Transplantation Nucleus removed from unfertilized egg and replaced with nucleus from diploid cell Develops into early embryo to derive ES cells

Induced Pluripotent Stem Cells Reprogramming of adult somatic cells to early embryonic-type state Induced by four specific transcription factors