Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer.

The natural history of small cell lung cancer (SCLC) includes rapid evolution from chemosensitivity to chemoresistance, although mechanisms underlying this evolution remain obscure due to scarcity of post-relapse tissue samples. We generated circulating tumor cell (CTC)-derived xenografts (CDXs) from SCLC patients to study intratumoral heterogeneity (ITH) via single-cell RNAseq of chemo-sensitive and -resistant CDXs and patient CTCs. We found globally increased ITH including heterogeneous expression of therapeutic targets and potential resistance pathways, such as EMT, between cellular subpopulations following treatment-resistance.

Klhl14 Antisense RNA is a Target of Key Skeletogenic Transcription Factors in the Developing Intervertebral Disc.

Study Design: RNA in situ hybridization (RISH) allows for validation and characterization of the long noncoding (lnc) natural antisense RNA (NAT) Klhl14as in the embryonic murine intervertebral disc (IVD) in the context of loss-of-function mutants for key transcription factors (TFs) in axial skeleton development.

Objective: Validation of Klhl14as in the developing murine IVD.

Summary Of Background Data: The IVD is a focus of regenerative medicine; however, processes and signaling cascades resulting in the different cell types in a mature IVD still require clarification in most animals including humans.

Isolation and 3D expansion of multipotent Sox9 mouse lung progenitors.

Multiple adult tissues are maintained by stem cells of restricted developmental potential which can only form a subset of lineages within the tissue. For instance, the two adult lung epithelial compartments (airways and alveoli) are separately maintained by distinct lineage-restricted stem cells. A challenge has been to obtain multipotent stem cells and/or progenitors that can generate all epithelial cell types of a given tissue.

An Integrative Developmental Genomics and Systems Biology Approach to Identify an In Vivo Sox Trio-Mediated Gene Regulatory Network in Murine Embryos.

Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the trio, namely, , , and , which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process.

A developmental transcriptomic analysis of and in embryonic intervertebral disc development.

and play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD) of the axial skeleton. They are conserved in mice and humans, whereby mutation/deficiency of human has been associated with kyphoscoliosis. By combining cell-type-specific transcriptome and ChIP-sequencing data, we identified the roles of / in cell proliferation, cartilage development and collagen fibrillogenesis, which are vital in early IVD morphogenesis.