Cell Lineage Determination in State Space A Systems View Brings Flexibility to Dogmatic Canonical Rules 英文参考文献.docVIP

Primer 1 CellLineageDeterminationinStateSpace:ASystems ViewBringsFlexibilitytoDogmaticCanonicalRules SuiHuang* InstituteforBiocomplexityandInformatics,UniversityofCalgary,Calgary,Canada Amodelofcell-typediversificationthatallowsforstochasticsamplingof available developmental states reconciles real-world observations with theseeminglyincongruentrulesofdeterministiccellfatedecisionmaking. ChoosingbetweenPrimitiveEndodermand Epiblast:NotBlackandWhite The article by Brickman and coworkers (Canham et al., this issueofPLoSBiology[11])isthelatestinarecentseriesofreports (reviewedin[12]and[13];[14–18])thathavebeguntochallenge the view that embryonic cells undergo a tightly controlled, predestined one-way journey from totipotency to pluripotency Thequestfortheoriginofdiversityinbiologyisasoldasthe disciplineitself.Muchasevolutionarybiologistssoughttofathom the diversification of life forms into discrete, self-maintaining species,developmentalbiologistsarenowtryingtounderstandthe diversificationofembryoniccellsintodiscrete,self-maintainingcell types of the multicellular body. This challenge revolves in large partaroundthefollowingquestions:howdoesthefertilizedegg—a singlecell—generateallcelllineages,includingthosethatbuildthe towards specific lineages. Brickman’s work undercuts this paradigm in two ways. First, it was long thought that inner cell mass (ICM)–derived ES cells cannot contribute to the primitive endoderm(PE),whichformsextra-embryonicendodermaltissues, suchastheyolksac—i.e.,thatEScellsarepluri-butnottotipotent [1]. Second, the deterministic view tacitly assumes that cells commit to a lineage because specific dedicated environmental signals (position in the embryo, cytokines, cell–cell interactions, etc.) instruct them to do so. Rather than following strict orders, however, ES cells may be capable of more flexible behaviour [19,20],suchthatrandomlyvacillatingEScells,whichinthiscase areexpectedtobecomeepiblast(precursoroftheembryoproper), may transiently entert