C H A P T E R
1 3
Differentiation: Environmental Factors,
Chemical and Cellular
C L I F F O R D G R O B S T E I N
Department of Biological Sciences, Stanford University,
Stanford, California, U.S.A.
The study of differentiation has been closely interlinked with the
techniques of cell, tissue and organ culture from their inception.
Students of development in the late nineteenth century recognized
the importance of separating differentiating cells from their surroundings and made deliberate, if largely ineffectual, efforts in the direction
of culture of isolated cells. At a later stage, developmentalists followed
the more successful experiments of the dedicated culturists with
keen interest. Embryological demonstrations of mosaic cleavage in
marine eggs, and the hypotheses of segregation of propagative determinants resulting from these and other observations, appeared to be in
harmony with the irreversibility and propagability of differentiation
claimed by tissue culturists. There resulted the mutually held dogma
of propagable fixity of differentiation which only in recent years has
again been brought into question (Trinkaus, 1956; Grobstein, 1959a,
1962a). In the new period of study of cytodifferentiation which now is
opening, it is clear that culture techniques will provide indispensable
tools for more precise analysis.
I shall make no effort here to review in detail earlier controversies and
I. Introduction
II. Criteria of Differentiation
III. Current Problems of Differentiation in vitro
IV. Cultural Factors and Differentiation
V. Homotypic Factors
V I . Heterotypic Factors
463
464
467
469
471
477
482
484
VII. Summary and Prospect
References
I. I N T R O D U C T I O N
1 3
Differentiation: Environmental Factors,
Chemical and Cellular
C L I F F O R D G R O B S T E I N
Department of Biological Sciences, Stanford University,
Stanford, California, U.S.A.
The study of differentiation has been closely interlinked with the
techniques of cell, tissue and organ culture from their inception.
Students of development in the late nineteenth century recognized
the importance of separating differentiating cells from their surroundings and made deliberate, if largely ineffectual, efforts in the direction
of culture of isolated cells. At a later stage, developmentalists followed
the more successful experiments of the dedicated culturists with
keen interest. Embryological demonstrations of mosaic cleavage in
marine eggs, and the hypotheses of segregation of propagative determinants resulting from these and other observations, appeared to be in
harmony with the irreversibility and propagability of differentiation
claimed by tissue culturists. There resulted the mutually held dogma
of propagable fixity of differentiation which only in recent years has
again been brought into question (Trinkaus, 1956; Grobstein, 1959a,
1962a). In the new period of study of cytodifferentiation which now is
opening, it is clear that culture techniques will provide indispensable
tools for more precise analysis.
I shall make no effort here to review in detail earlier controversies and
I. Introduction
II. Criteria of Differentiation
III. Current Problems of Differentiation in vitro
IV. Cultural Factors and Differentiation
V. Homotypic Factors
V I . Heterotypic Factors
463
464
467
469
471
477
482
484
VII. Summary and Prospect
References
I. I N T R O D U C T I O N