Figure 1.
The scheme, phase diagram and intrinsic potential landscape of cell type switchings.
A: The scheme of dedifferentiation (including reprogramming and differentiation) and transdifferentiation. B: A model for the gene circuit for cell development. C: The phase diagram for the gene circuit with . D: The cell fate landscape
obtained from the Hamilton-Jacobi equation versus
and
, and the phase diagram was drawn on the intrinsic potential landscape with stable states represented by black solid lines and unstable states represented by black dash line. The red dash lines represent the dedifferentiation(reprogramming) and redifferentiation process while the yellow solid lines represents the transdifferentiation process. (
,
,
.)
Figure 2.
The gene circuits of mutual antagonism and self activation.
A: The interaction of and
in determining myeloid cell or erythroid cell,
and
in determining inner cell mass or trophectoderm,
and
in determining epiblast or primitive endoderm. B: Scheme for the gene circuit of B cell to macrophage conversion. The dashed lines indicate uncertainty. C: Scheme for the gene circuit in determining mesendodermal and ectodermal.
Figure 3.
The dynamics of super-critical and sub-critical bifurcations for cell type switchings.
A: The phase diagram for changing the parameter with
. B: The phase diagram for changing the parameter
with
. C: The quantified dedifferentiation and differentiation landscape and pathways for continuous changing parameter
with
. D: The quantified dedifferentiation and differentiation landscape and pathways for continuous changing parameter
with
.
Figure 4.
The dynamics of transdifferentiation undergoing an intermediate state.
A: The phase diagram for decreasing induced the differentiated state
to the other differentiated state
through the intermediate state
. (
,
) B: The barrier heights of the population landscape versus the parameter
. C: The quantified transdifferentiation landscape and pathways for continuous changing parameter
.
Figure 5.
The dynamics of transdifferentiation undergoing a series of unstable states.
A: The phase diagram for decreasing induced the differentiated state
to the other differentiated state
. (
,
) B: The barrier heights of the population landscape versus the parameter
. C: The quantified transdifferentiation landscape and pathways for continuous changing parameter
.
Figure 6.
The dynamics of dedifferentiation undergoing a pluripotent state.
A: The phase diagram for decreasing induced the differentiated state
to the other differentiated state
through the pluripotent state
. (
,
) B: The barrier heights of the population landscape versus the parameter
. C: The quantified dedifferentiation landscape and pathways for continuous changing parameter
.
Figure 7.
The barrier height, escape time and dissipation rate for different self activation strength with mutual repression strength
under fluctuations.
A: The intrinsic barrier height versus
. B: The intrinsic barrier height
versus the population barrier height
in
for
and
. C: The escape time
from the valley
versus the intrinsic barrier height
. D: The dissipation rate versus the decreasing parameter
.
Figure 8.
The paths of cell type switchings with different self activation strength .
The paths of differentiation (A,B), dedifferentiation (A,B) and transdifferentiation (C,D) for different in zero-limit fluctuations on the intrinsic potential
. Purple arrows represent the intrinsic flux velocity (
) while the white arrows represent the negative gradient of intrinsic potential (
)).
Figure 9.
The phase diagram, barrier height, probability of the dominant path and mean first passaging time for different mutual repression strength .
A: The phase diagram for changing mutual repression strength with
. B: The barrier heights versus the parameter
. C: The probability of the dominant path through the progenitor cell state
divided that of the path through the intermediate state
versus the inhibition strength
. D: The mean first passaging time through the two paths versus the inhibition strength
.
Figure 10.
The flux on the population potential landscape.
The flux on the population potential landscape with . Purple arrows represent the flux (
) while the black arrows represent the negative gradient of population potential landscape (
)) for
,
(A),
(B),
(C). The black lines represent the pathways from state
to state
while the purple lines represent the pathways from state
to state
.
Figure 11.
Mean first passage time versus barrier height with different mutual repression strength .
A: The logarithm of the mean first passage time (MFPT) versus the barrier heights according to Figure 4(B). B: The logarithm of the mean first passage time (MFPT) versus the barrier heights according to Figure 5(B).