Biology subjects

Jiao, A.

Publications and source records attributed to Jiao, A..

4 recordsLinked to original sources

bioRxiv2025

Development of a Synthetic Hydrogel to Foster Microvascularization of an Endometriosis Microphysiological System

The ascent of novel alternative methods (NAMs) in drug development spotlights the dual needs for improved biological fidelity to in vivo along with reproducibility, especially in regulatory applications. The need for pre-clinical models of patient-derived endometriosis lesions motivates development of a vascularizable completely synthetic extracellular matrix (v-CS-ECM) that supports morphogenesis of perfusable microvasculature in a microfluidic device, in the context of relevant lesion cells. This paper describes v-CS-ECM, a peptide-modified polyethylene glycol-based hydrogel crosslinked with a cell-degradable peptide that achieves these dual goals. Vessels form by morphogenesis after the liquid v-CS-ECM precursor, containing endothelial cells and fibroblasts, is injected into the tissue compartment to encapsulate cells. Vessel formation is influenced by ECM biochemical and biophysical properties, source of vascular cells, and microphysiological system (MPS) operating conditions. The v-CS-ECM also supports co-culture of endometrial epithelial organoids (EEOs) and fibroblasts, and formation of microvascularized endometriosis lesion-like structures when all cell types are co-encapsulated in a microfluidic device with constant flow. Hence, v-CS-ECM overcomes limitations of reproducibility and biological function inherent in the fibrin-based ECM typically employed for microvascular morphogenesis, as well as Matrigel for organoid culture, thus offering promise for NAMs evaluating endometriosis drugs in the preclinical setting.

bioengineering↗

bioRxiv2021

Zinc finger protein Zfp335 controls early T cell development and survival through beta-selection-dependent and -independent mechanisms

T cell development in the thymus undergoes the process of differentiation, selective proliferation and survival from CD4-CD8- double negative (DN) stage to CD4+CD8+ double positive (DP) stage prior to the formation of CD4+ helper and CD8+ cytolytic T cells ready for circulation. Each developmental stage is tightly regulated by sequentially-operating molecular networks, of which only limited numbers of transcription regulators have been deciphered. Here we identified Zfp335 transcription factor as a new player in the regulatory network controlling thymocyte development. We demonstrate that Zfp335 intrinsically controls DN to DP transition, as T cell-specific deficiency in Zfp335 leads to a substantial accumulation of DN3 along with reduction of DP, CD4+ and CD8+ thymocytes. This developmental blockade at DN stage results from the impaired intracellular TCR{beta} expression as well as increased susceptibility to apoptosis in thymocytes. Transcriptomic and ChIP-seq analyses revealed a direct regulation of transcription factors Bcl6 and Rorc by Zfp335. Importantly, enhanced expression of TCR{beta} and Bcl6/Ror{gamma}T restores the developmental defect during DN3 to DN4 transition and improves thymocytes survival, respectively. These findings identify a critical role of Zfp335 in controlling T cell development by maintaining intracellular TCR{beta} expression-mediated {beta}- selection and independently activating cell survival signaling.

immunology↗

bioRxiv2021

Single-cell sequencing characterizes intratumoral profile of immune cells in old mice

It has long been thought that aging is a major risk factor for cancer incidence. However, accumulating evidence indicates increased resistance of old animals to tumor growth. A systematic understanding of how old individuals defend against tumor invasion is currently lacking. Here we investigated the differences of age-associated alterations in tumor-infiltrating immune cells between young and old mice using single-cell RNA analysis. Our results showed that a higher proportion of cytotoxic CD8+ T cells, nTregs, cDC, and M1-type macrophages, while a higher percentage of exhausted CD8+ T cells, iTregs, pDC, and M2-type macrophages were found in young mice. Importantly, TCR diversity analysis showed top 10 TCR clones consisted primarily of exhausted CD8+ T cells in young mice whereas tip clones were predominantly cytotoxic CD8+ T cells in old mice. Consistently, trajectory inference demonstrated that CD8+ T cells preferentially differentiated into cytotoxic cells in old mice in contrast to exhausted cells in young mice. Meanwhile, we confirmed the main distinctions between young and old mice by flow cytometry. Collectively, our data revealed that a significantly higher proportion of effector immune cells in old mice defend against tumor progression, providing a framework for the immunotherapy of elderly patients with tumors.

immunology↗

bioRxiv2019

Auditory Cortex Tracks Masked Acoustic Onsets in Background Speech: Evidence for Early Cortical Stream Segregation

Humans are remarkably skilled at listening to one speaker out of an acoustic mixture of several speech sources. Two speakers are easily segregated, even without binaural cues, but the neural mechanisms underlying this ability are not well understood. One possibility is that early cortical processing performs a spectro-temporal decomposition of the acoustic mixture, allowing the attended speech to be reconstructed via optimally weighted recombinations that discount spectro-temporal regions where sources heavily overlap. Using human magnetoencephalography (MEG) responses to a two-talker mixture, we show evidence for an alternative possibility, in which early, active segregation occurs even for strongly spectro-temporally overlapping regions. Early ([~]70 ms) responses to non-overlapping spectro-temporal features are seen for both talkers. When competing talkers spectro-temporal features mask each other, the individual representations persist, but they occur with a [~]20 ms delay. This suggests that the auditory cortex recovers acoustic features that are masked in the mixture, even if they occurred in the ignored speech. The existence of such noise-robust cortical representations, of features present in attended as well as ignored speech, suggests an active cortical stream segregation process, which could explain a range of behavioral effects of ignored background speech.

neuroscience↗