TY - JOUR
T1 - Dynamic conversion of cell sorting patterns in aggregates of embryonic stem cells with differential adhesive affinity
AU - Tse, Jeffrey D.
AU - Moore, Robert
AU - Meng, Yue
AU - Tao, Wensi
AU - Smith, Elizabeth R.
AU - Xu, Xiang Xi
N1 - Funding Information:
We are grateful to the doctoral dissertation committee members for Jeffrey Tse and additional colleagues, including Drs. Pedro Salas, Valery Shestopalov, Daniel Pelaez, and Sophia George, for their suggestions and ideas during the course of the study. We acknowledge the excellent technical assistance from the Transgenic Facility, Animal Facility, and Imaging Core at the University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center.
Funding Information:
The study was partially supported by internal funding from University of Miami/Sylvester Comprehensive Cancer Center, and the University Scientific Award Committee (SAC) pilot fund. Prior grants R01 CA230916; R01 CA095071, R01 CA099471, and R01 CA79716 to X.X. Xu from NCI, NIH also contributed to the work. The funders had no input on the design, analysis, interpretation, and preparation of the manuscript.
PY - 2021/12
Y1 - 2021/12
N2 - Background: Mammalian early development comprises the proliferation, differentiation, and self-assembly of the embryonic cells. The classic experiment undertaken by Townes and Holtfreter demonstrated the ability of dissociated embryonic cells to sort and self-organize spontaneously into the original tissue patterns. Here, we further explored the principles and mechanisms underlying the phenomenon of spontaneous tissue organization by studying aggregation and sorting of mouse embryonic stem (ES) cells with differential adhesive affinity in culture. Results: As observed previously, in aggregates of wild-type and E-cadherin-deficient ES cells, the cell assemblies exhibited an initial sorting pattern showing wild-type cells engulfed by less adhesive E-cadherin-deficient ES cells, which fits the pattern predicted by the differential adhesive hypothesis proposed by Malcom Steinberg. However, in further study of more mature cell aggregates, the initial sorting pattern reversed, with the highly adhesive wild-type ES cells forming an outer shell enveloping the less adhesive E-cadherin-deficient cells, contradicting Steinberg’s sorting principle. The outer wild-type cells of the more mature aggregates did not differentiate into endoderm, which is known to be able to sort to the exterior from previous studies. In contrast to the naive aggregates, the mature aggregates presented polarized, highly adhesive cells at the outer layer. The surface polarity was observed as an actin cap contiguously spanning across the apical surface of multiple adjacent cells, though independent of the formation of tight junctions. Conclusions: Our experimental findings suggest that the force of differential adhesive affinity can be overcome by even subtle polarity generated from strong bilateral ligation of highly adhesive cells in determining cell sorting patterns.
AB - Background: Mammalian early development comprises the proliferation, differentiation, and self-assembly of the embryonic cells. The classic experiment undertaken by Townes and Holtfreter demonstrated the ability of dissociated embryonic cells to sort and self-organize spontaneously into the original tissue patterns. Here, we further explored the principles and mechanisms underlying the phenomenon of spontaneous tissue organization by studying aggregation and sorting of mouse embryonic stem (ES) cells with differential adhesive affinity in culture. Results: As observed previously, in aggregates of wild-type and E-cadherin-deficient ES cells, the cell assemblies exhibited an initial sorting pattern showing wild-type cells engulfed by less adhesive E-cadherin-deficient ES cells, which fits the pattern predicted by the differential adhesive hypothesis proposed by Malcom Steinberg. However, in further study of more mature cell aggregates, the initial sorting pattern reversed, with the highly adhesive wild-type ES cells forming an outer shell enveloping the less adhesive E-cadherin-deficient cells, contradicting Steinberg’s sorting principle. The outer wild-type cells of the more mature aggregates did not differentiate into endoderm, which is known to be able to sort to the exterior from previous studies. In contrast to the naive aggregates, the mature aggregates presented polarized, highly adhesive cells at the outer layer. The surface polarity was observed as an actin cap contiguously spanning across the apical surface of multiple adjacent cells, though independent of the formation of tight junctions. Conclusions: Our experimental findings suggest that the force of differential adhesive affinity can be overcome by even subtle polarity generated from strong bilateral ligation of highly adhesive cells in determining cell sorting patterns.
KW - Adhesive
KW - Apical polarity
KW - Cell sorting
KW - Cell spontaneous assembly
KW - Differential adhesion hypothesis
KW - Differential adhesive hypothesis
KW - E-cadherin
KW - Embryoid body
KW - Embryonic development
KW - Embryonic stem (ES) cells
KW - Morphogenesis
KW - Self-assembly
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U2 - 10.1186/s12861-020-00234-0
DO - 10.1186/s12861-020-00234-0
M3 - Article
AN - SCOPUS:85098796755
VL - 21
JO - BMC Developmental Biology
JF - BMC Developmental Biology
SN - 1471-213X
IS - 1
M1 - 2
ER -