Stem cells, pluripotency, Yamanaka factors, regeneration, organoids, dedifferentiation.
Stem Cells And Development Principles
Stem cell
Undifferentiated cell with dual capacity: self-renewal (divide to produce daughter stem cells) + differentiation into specialised cell…
Embryonic stem cell (ESC)
Pluripotent cell from inner cell mass of blastocyst (Evans-Kaufman-Martin 1981). Can differentiate into all three germ layers; maintained…
Induced pluripotent stem cell (iPSC)
Somatic cell reprogrammed to pluripotency by ectopic Yamanaka factors (Oct4, Sox2, Klf4, c-Myc). Takahashi-Yamanaka 2006 (mouse), 2007…
Yamanaka factors
Core pluripotency transcription factors OSKM: Oct4, Sox2, Klf4, c-Myc. Sufficient to reprogram fibroblasts to iPSCs; c-Myc replaceable…
Adult (tissue) stem cell
Multipotent/unipotent stem cell in adult tissue niche: HSC (blood), satellite cell (muscle), Lgr5+ crypt-base cell (intestine), neural stem…
Organoid
3D self-organising miniature organ grown from stem cells in Matrigel. Recapitulates crypt-villus (intestine), nephron (kidney), cortex…
Tissue regeneration
Restoration of lost/damaged tissue. Epimorphic (blastema formation: salamander limb, zebrafish fin) vs morphallactic (remodelling without…
Hematopoietic stem cell
Bone-marrow self-renewing cell giving rise to all blood lineages. First stem cell characterised (Till & McCulloch 1961). Foundation of BM…
Stem cell niche
Tissue microenvironment maintaining stem-cell self-renewal + quiescence (Schofield 1978). Signals: Wnt, Notch, BMP, direct contact with…
Direct lineage reprogramming
Transdifferentiation: forcing one differentiated cell type into another without iPSC intermediate via transcription-factor cocktails…
Waddington epigenetic landscape
Waddington 1957: cell fate as ball rolling down branching potential surface V(x) on gene-expression manifold; differentiation = gradient…
Clonal dynamics neutral drift
Klein-Simons (2011) stem-cell-niche model: equipotent stem cells follow neutral Markov birth-death with stochastic loss/replacement;…
HSC (Till-McCulloch 1961)
Till-McCulloch 1961 spleen-colony assay; first stem-cell concept; modern HSC-niche Schofield 1978.
iPSC (Yamanaka 2006)
S Yamanaka 2006 (Nobel 2012) OSKM-factor reprogramming; modern integration-free + chemical-iPSC + clinical-grade.
Waddington landscape (1957)
C Waddington 1957 epigenetic-landscape; modern computational reconstruction Bhattacharya 2011 + Wang 2010 quasi-potential.
ES cell (Evans-Kaufman 1981)
Evans-Kaufman 1981 + Martin 1981 mouse-ES cells (Evans Nobel 2007); modern Thomson 1998 hES; clinical hES therapies 2010s.
Organoids (Clevers 2009)
H Clevers 2009 intestinal-organoids Lgr5+; modern brain + lung + kidney + tumor organoids; precision-medicine + drug-screening.
Niche (Schofield 1978)
R Schofield 1978 stem-cell-niche concept; modern HSC + ISC + neural-stem-cell niche imaging + functional perturbation.
iPSC (Yamanaka 2006)
S Yamanaka 2006 (Nobel 2012) Oct4-Sox2-Klf4-Myc reprogramming; modern modern iPSC-derived disease-models + 2024 transplantation trials.
ES cells (Evans-Kaufman 1981)
M Evans-M Kaufman 1981 (Evans Nobel 2007) mouse-ES-cell + Thomson 1998 hES; modern modern Smith naive-pluripotency + 2024 hES.
HSC (Till-McCulloch 1961)
J Till-E McCulloch 1961 hematopoietic-stem-cell CFU-S; modern modern Weissman 1988 + Bhattacharya 2024 single-cell-fate-mapping.
Organoid (Clevers 2009)
H Clevers 2009 intestinal-organoid Lgr5+; modern brain + lung + kidney + liver + 2024 vascularized + Asexual-development atlas.
PDX (De Bono 2012)
J De Bono 2012 + Hidalgo 2014 patient-derived-xenograft; modern modern humanized-mouse + organoid-PDX + 2024 immune-PDX co-culture.
Thomson hES (1998)
J Thomson 1998 first human-ES; modern modern derivatives + ips alternative ethical + 2024 SCNT + fertility-clinic blastocyst.