|
| Status |
Public on Apr 02, 2021 |
| Title |
High proliferation and delamination during skin epidermal stratification |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The development of complex stratified epithelial barriers in mammals is initiated from single-layered epithelia. How stratification is initiated and fueled are still open questions. Previous studies on skin epidermal stratification suggested a central role for perpendicular/asymmetric cell division orientation of the basal keratinocyte progenitors. Here, we use centrosomes, that organize the mitotic spindle, to test whether cell division orientation and stratification are linked. Genetically ablating centrosomes from the developing epidermis leads to the activation of the p53-, 53BP1- and USP28-dependent mitotic surveillance pathway causing a thinner epidermis and hair follicle arrest. The centrosome/p53-double mutant keratinocyte progenitors significantly alter their division orientation in the later stages without majorly affecting epidermal differentiation. Together with time-lapse imaging and tissue growth dynamics measurements, the data suggest that the first and major phase of epidermal development is boosted by high proliferation rates in both basal and suprabasally-committed keratinocytes as well as cell delamination, whereas the second phase maybe uncoupled from the division orientation of the basal progenitors. The data provide insights for tissue homeostasis and hyperproliferative diseases that may recapitulate developmental programs.
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| |
|
| Overall design |
RNA-Seq analysis from mRNA of primary keratinocytes at P0 or skin epidermis at E13.5 with K14-Cre-specific depletion of Sas-4 and controls. Four replicates for each condition were used.
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| |
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| Contributor(s) |
Bazzi H, Damen M |
| Citation(s) |
34050161 |
| |
| Submission date |
Nov 12, 2020 |
| Last update date |
Jul 02, 2021 |
| Contact name |
Hisham Bazzi |
| Organization name |
University Hospital Cologne
|
| Department |
CECAD & Dermatology
|
| Lab |
Bazzi Lab
|
| Street address |
Joseph-Stelzmann-Straße 26
|
| City |
Cologne |
| State/province |
NRW |
| ZIP/Postal code |
50931 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (16)
|
| GSM4906371 |
primary mouse epidermal keratinocytes_P0_Sas-4_ control_1 |
| GSM4906372 |
primary mouse epidermal keratinocytes_P0_Sas-4_ control_2 |
| GSM4906373 |
primary mouse epidermal keratinocytes_P0_Sas-4_ control_3 |
| GSM4906374 |
primary mouse epidermal keratinocytes_P0_Sas-4_ control_4 |
| GSM4906375 |
primary mouse epidermal keratinocytes_P0_Sas-4_ mutant_1 |
| GSM4906376 |
primary mouse epidermal keratinocytes_P0_Sas-4_ mutant_2 |
| GSM4906377 |
primary mouse epidermal keratinocytes_P0_Sas-4_ mutant_3 |
| GSM4906378 |
primary mouse epidermal keratinocytes_P0_Sas-4_ mutant_4 |
| GSM4906379 |
embryonic skin epidermis_E13.5_Sas-4_ control_1 |
| GSM4906380 |
embryonic skin epidermis_E13.5_Sas-4_ control_2 |
| GSM4906381 |
embryonic skin epidermis_E13.5_Sas-4_ control_3 |
| GSM4906382 |
embryonic skin epidermis_E13.5_Sas-4_ control_4 |
| GSM4906383 |
embryonic skin epidermis_E13.5_Sas-4_ mutant_1 |
| GSM4906384 |
embryonic skin epidermis_E13.5_Sas-4_ mutant_2 |
| GSM4906385 |
embryonic skin epidermis_E13.5_Sas-4_ mutant_3 |
| GSM4906386 |
embryonic skin epidermis_E13.5_Sas-4_ mutant_4 |
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| Relations |
| BioProject |
PRJNA677993 |
| SRA |
SRP292409 |
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