Biology subjects

Khan, H. A.

Publications and source records attributed to Khan, H. A..

4 recordsLinked to original sources

bioRxiv2021

Efficient differentiation of human primordial germ cells through geometric control reveals a key role for NODAL signaling

Human primordial germ cells (hPGCs) form around the time of implantation and are the precursors of eggs and sperm. Many aspects of hPGC specification remain poorly understood. Here we show that micropatterned human pluripotent stem cells (hPSCs) treated with BMP4 give rise to hPGC-like cells (hPGCLC) and use these as a quantitatively reproducible and simple in vitro model to interrogate this important developmental event. We characterize micropatterned hPSCs up to 96h for the first time and show that hPGCLC populations are stable and continue to mature. By perturbing signaling during hPGCLC differentiation, we identify a previously unappreciated role for NODAL signaling and find that the relative timing and duration of BMP and NODAL signaling are critical parameters controlling the number of hPGCLCs. We formulate a mathematical model for a network of cross-repressive fates driven by NODAL and BMP signaling which predicts the measured fate patterns after signaling perturbations. Finally, we show that hPSC colony size dictates the efficiency of hPGCLC specification, which led us to dramatically improve the efficiency of hPGCLC differentiation over current protocols.

developmental biology↗

bioRxiv2021

Expanding the Potential Genes of Inborn Errors of Immunity through Protein Interactions

Inborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity. Here we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types.

immunology↗

bioRxiv2021

A Creb3-Like Transcription Factor Coordinates ER Function uponFood Intake to Regulate Lipid Metabolism

Ingestion of nutrients elicits essential physiological responses, including absorption, digestion, cessation of feeding and nutrient storage. The endoplasmic reticulum (ER) is central to this nutritional homeostasis, since it regulates intracellular organelle function, drives intercellular communication and promotes metabolite distribution. We identified the Drosophila Creb3L-family transcription factor, CrebA, as the key metabolic regulator of ER function, thereby affecting lipid metabolism and feeding behavior. In response to feeding, CrebA activity is rapidly and transiently activated. CrebA directly drives the expression of the ER protein sorting machinery. We demonstrate that CrebA levels regulate lipid metabolism through lipoprotein secretion into the hemolymph and suppress feeding behavior. Further, CrebA mouse homologs are also upregulated in the liver following feeding and drive the transcriptional activation of ER protein sorting machinery genes in mammals. Our results reveal an evolutionarily conserved transcription switch which is turned on in response to food ingestion and orchestrates a negative feedback loop that promotes satiety by regulating ER function and protein secretion.

cell biology↗

bioRxiv2020

Effect of leaf temperature on estimating physiological traits of wheat leaves from hyperspectral reflectance

A growing number of leaf traits can be predicted from hyperspectral reflectance data. These include structural and compositional traits, such as leaf mass per area, nitrogen and chlorophyll content, but also physiological traits such a Rubisco carboxylation activity, electron transport rate and respiration rate. Since physiological traits vary with leaf temperature, how does this impact on predictions made from reflectance measurements? We investigated this with two wheat varieties, by repeatedly measuring each leaf through a sequence of temperatures imposed by varying the air temperature in a growth room. The function predicting Rubisco capacity normalised to 25 {degrees}C predicted the same value, regardless of leaf temperatures ranging from 20 to 35{degrees}C. Leaf temperature affected none of the predicted traits: Vcmax25, J, chlorophyll content, LMA, N content per unit leaf area or Vcmax25/N. However, as others have derived models to predict Rubisco activity that includes variation associated with leaf temperature, we discuss whether these functions may include a temperature signal within the reflectance spectra.

plant biology↗