Biology subjects

Wermke, M.

Publications and source records attributed to Wermke, M..

2 recordsLinked to original sources

bioRxiv2018

Comparative RNAi Screens in Isogenic Human Stem Cells Reveal SMARCA4 as a Differential Regulator

Large-scale RNAi screens are a powerful approach to identify functions of genes in a cell-type specific manner. For model organisms, genetically identical (isogenic) cells from different cell-types are readily available, making comparative studies meaningful. For humans, however, screening isogenic cells is not straightforward. Here, we show that RNAi screens are possible in genetically identical human stem cells, employing induced pluripotent stem cell as intermediates. The screens revealed SMARCA4 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) as a stemness regulator, while balancing differentiation distinctively for each cell type. SMARCA4 knockdown in hematopoietic stem progenitor cells (HSPC) caused impaired self-renewal in-vitro and in-vivo with skewed myeloid differentiation; whereas in neural stem cells (NSC), it impaired selfrenewal while biasing differentiation towards neural lineage, through combinatorial SWI/SNF subunit assembly. Our findings pose a powerful approach for deciphering human stem cell biology and attribute distinct roles to SMARCA4 in stem cell maintenance.

molecular biology↗

bioRxiv2017

Continuous high-resolution in vivo imaging reveals tumor-specific dissemination in an embryonic zebrafish xenograft model

Mechanisms mediating tumor metastasis are crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track injected human leukemic and breast cancer cells in real time using selective plane illumination microscopy (SPIM) for up to 30 hours. Injected cells exhibited disease-specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells. While breast cancer cells predominantly adhered to nearby regions, about 30% invaded the avascularized tissue, reminiscent of their metastatic phenotype. Survival of the injected tumor cells was partly inhibited by the cellular innate immune system of the recipient embryos and leukemic cell dissemination was effectively inhibited by pharmacological ROCK1 blockade. These observations, and the ability to image several embryos simultaneously, support the use of eZXM and SPIM imaging as a functional screening platform to identify compounds that restricts cancer cell spread and invasion.

cancer biology↗