Biology subjects

Chawla, P.

Publications and source records attributed to Chawla, P..

3 recordsLinked to original sources

bioRxiv2023

MRTF activity in breast cancer cells promotes osteoclastogenesis through a paracrine action of CTGF

Bone is a frequent site for breast cancer metastasis. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL (receptor activator for nuclear factor {kappa}B)-induced differentiation of bone marrow-derived macrophages (BMDMs) to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that Myocardin-related transcription factor (MRTF) in breast cancer cells plays an important role in paracrine modulation of RANKL-induced osteoclast differentiation. This is partly attributed to MRTFs critical role in maintaining the basal cellular expression of connective tissue growth factor (CTGF), findings that align with a strong positive correlation between CTGF expression and MRTF-A gene signature in the human disease context. Luminex analyses reveal that MRTF depletion in breast cancer cells has a broad impact on OCL-regulatory cell-secreted factors that extend beyond CTGF. Experimental metastasis studies demonstrate that MRTF depletion diminishes OCL abundance and bone colonization breast cancer cells in vivo, suggesting that MRTF inhibition could be an effective strategy to diminish OCL formation and skeletal involvement in breast cancer. In summary, this study highlights a novel tumor-extrinsic function of MRTF relevant to breast cancer metastasis. SIGNIFICANCE STATEMENTO_LIMRTF, a transcriptional coactivator of SRF, is known to promote breast cancer progression through its tumor-cell-intrinsic function. Whether and how MRTF activity in tumor cells modulates other types of cells in the tumor microenvironment are not clearly understood. C_LIO_LIThis study uncovers a novel tumor-cell-extrinsic function of MRTF in breast cancer cells in promoting osteoclast differentiation partly through CTGF regulation, and further demonstrates MRTFs requirement for bone colonization of breast cancer cells in vivo. C_LIO_LIOur studies suggest that MRTF inhibition could be an effective strategy to diminish osteoclast formation and skeletal involvement in metastatic breast cancer. C_LI

cancer biology↗

bioRxiv2022

Differential representation of natural and manmade images in the human ventral visual stream

AO_SCPLOWBSTRACTC_SCPLOWThe human visual cortex processes visual stimuli hierarchically. Early visual areas (V1, V2) of the ventral visual stream feed crude visual features (like orientation and edges) into later visual areas (V4, lateral occipital (Lat Occ), inferior temporal (IT)) that then encode complex visual features (like object form). Previous studies have reported a difference in fMRI responses between natural and urban landscapes in certain parts of the brain. Here we asked if this distinction in the representation of complex natural and man-made visual stimuli extends to the ventral visual stream and if state-of-the-art convolutional neural networks (CNN) provide a map to this categorical distinction. To assess this, we used an open source fMRI data set of V1-4 and LatOcc BOLD responses to 1750 passively viewed natural and man-made grayscale images. The same images were fed into the pre-trained CORnet-S, a CNN designed to model hierarchical human visual processing layer-wise. To identify differences in representations within and between the human visual cortex and the CNN, we computed representational dissimilarity matrices. The BOLD response to the manmade and natural images shows correlation differences for the two categories, which increase across V4 and LatOcc. Such differences were also observed in the model CORnet-S for the layers V4 and IT. Our results suggest that the human visual cortex processes natural and manmade images differently starting from V4 and that this representational difference is modeled in CORnet-S. In both, categorical representation is progressively established in the later processing stages. This might indicate that the brain has perhaps developed two-distinct systems for their representations which can be directed through evolution. Further analysis may elucidate the contributory role of evolution towards this paradigm.

neuroscience↗

bioRxiv2021

A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ cells to diabetes recovery in zebrafish

Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we use single-cell transcriptomics to map de novo {beta}-cell regeneration during induction and recovery from diabetes in zebrafish. We show that the zebrafish has evolved two distinct types of somatostatin-producing {delta}-cells, which we term {delta}1- and {delta}2-cells. Moreover, we characterize a small population of glucose-responsive islet cells, which share the hormones and fate-determinants of both {beta}- and {delta}1-cells. The transcriptomic analysis of {beta}-cell regeneration reveals that {beta}/{delta} hybrid cells constitute a prominent source of insulin-expression during diabetes recovery. Using in vivo calcium imaging and cell tracking, we further show that the hybrid cells form de novo and acquire glucose-responsiveness in the course of regeneration. The overexpression of dkk3, a gene enriched in hybrid cells, increases their formation in the absence of {beta}-cell injury. Finally, interspecies comparison shows that plastic {delta}1-cells are partially related to PP-cells in the human pancreas. Our work provides an atlas of {beta}-cell regeneration and indicates that the rapid formation of glucose-responsive hybrid cells contributes to the resolution of diabetes in zebrafish

developmental biology↗