Search PubMedSearch

SEARCH · Search PubMed

Results for “stress responses”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Genome-wide characterization of ZmCRY genes: unveiling stress response mechanisms and the role of ZmCRYPHR2 in salinity tolerance.

BACKGROUND: Blue light serves as a crucial environmental signal regulating plant growth and development. The cryptochrome (CRY) family represents a key class of blue light receptors involved in these processes, as well as plant growth, development, and defense. However, the functions of CRYs in maize remain largely unexplored. RESULTS: In this study, nine ZmCRY genes were identified and found to be unevenly distributed across five chromosomes. Gene structure and conserved motif analyses revealed that ZmCRYs within the same phylogenetic groups are highly conserved. Synteny analysis indicated a close evolutionary relationship between ZmCRYs and their homologs in Oryza sativa. Promoter analysis identified diverse cis-regulatory elements linked to light response, stress tolerance, and hormone signaling. RT-qPCR analysis showed that ZmCRYs respond to various abiotic and biotic stresses, including high salinity, drought, nitrogen deficiency, Fusarium verticillioides, and Puccinia polysora. Functional studies demonstrated that ZmCRYPHR2, localized in chloroplasts and the cytoplasmic membrane, plays a role in scavenging reactive oxygen and regulating maize salt tolerance. Haplotype 2 of ZmCRYPHR2 was identified as the preferred haplotype in a panel of 269 inbred lines. CONCLUSIONS: These findings provide a comprehensive genomic and functional characterization of the ZmCRY gene family, with ZmCRYPHR2 identified as a pivotal regulator of salt tolerance, offering valuable genetic insights for the development of stress-resilient maize breeding.

Zea mays

Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response.

Cells rapidly and extensively remodel their transcriptome in response to stress to restore homeostasis, but the underlying mechanisms are not fully understood. Here, we characterize the dynamic changes in transcriptome, epigenetics, and 3D genome organization during the integrated stress response (ISR). ISR induction triggers widespread transcriptional changes within 6 h, coinciding with increased binding of ATF4, a key transcriptional effector. Notably, ATF4 binds to hundreds of genes even under non-stress conditions, priming them for stronger activation upon stress. The transcriptional changes at ATF4-bound sites during ISR do not rely on increased H3K27 acetylation, chromatin accessibility, or rewired enhancer-promoter looping. Instead, ATF4-mediated gene activation is linked to the redistribution of CEBPγ from non-ATF4 sites to a subset of ATF4-bound regions, likely by forming an ATF4/CEBPγ heterodimer. CEBPγ preferentially targets the sites pre-occupied by ATF4, as well as genomic regions exhibiting a unique higher-order chromatin structure signature. Thus, the transcriptional responses during ISR are largely pre-wired by intrinsic chromatin properties. These findings provide critical insights into transcriptional remodeling during ISR with broader implications for other stress responses.

Activating Transcription Factor 4

Twenty-Five Years of the Environmental Stress Response and the Enduring Power of Yeast in Stress Biology.

All organisms must be able to sense and respond to adverse environments, especially those that threaten cellular integrity. The age of genomics clarified the breadth and specificity of cellular stress responses, including in free-living microbes directly exposed to a changing environment. The environmental stress response (ESR) in Saccharomyces cerevisiae was among the first responses defined at the transcriptome-wide level as a common program triggered by diverse types of stress. Since its original publication over 25 years ago, many studies have explored the role, regulation, and evolution of the ESR and underlying principles of stress defense. This perspective reviews the history of the ESR, recent insights and perspectives into its purpose and regulation, and remaining questions in stress biology primed for the power of yeast experimentation.

Saccharomyces cerevisiae

Genome-wide mapping of stress-responsive lncRNA, uc.104, reveals the chromatin-mediated regulation of stress and plasticity-related genes in the hippocampus of chronic restraint rats.

Chronic stress significantly impacts hippocampal function through transcriptional and epigenetic mechanisms. While the roles of lncRNAs in stress-related transcriptional and epigenetic regulation have recently been recognized, their genome-wide functions controlling the transcriptional network remain largely unclear. Evidence indicates that the lncRNA uc.104 is involved in stress responses; however, its genome-wide chromatin interactions and gene regulatory effects are yet to be explored. To examine this, we combined chromatin isolation by RNA purification sequencing (ChIRP-seq) and RNA sequencing (RNA-seq) in the hippocampus from handled control and chronic restraint stress (CRS) rats. ChIRP-seq identified 6,664 uc.104 binding peaks under CRS, including 6,517 enriched and 149 reduced. Many peaks were mapped to intronic and promoter-proximal regions of protein-coding genes. Integration of ChIRP-seq with RNA-seq data revealed 1,839 differentially expressed genes associated with uc.104 binding sites, with 106 high-confidence overlaps. Several genes (Gabra3, Htr7, Irs1, Gpr37, Clu, Hspa1b, Ppp3r2, Nfasc, Pcdhac2, and Cysltr2) identified as regulatory targets of uc.104, have been directly implicated in stress responses, synaptic plasticity, and neuroinflammation. Gene ontology and Synapse GO (SynGO) analyses revealed significant enrichment for processes involving dendritic spine formation, synapse organization, and pre- and postsynaptic signaling. Protein-protein interaction analysis identified hub genes, including EGFR, CDC42, IGF1R, CTNNB1, CALM1, CALM3, POLR2A, MDM2, TBP, and CSNK1E, several of which have been linked to stress-responsive pathways. Together, our findings reveal that uc.104 binding to chromatin near stress- and synapse-related genes may act as a regulator of stress-responsive transcriptional networks in the hippocampus. By linking uc.104 occupancy to stress and synaptic responsive genes, this study highlights uc.104 as a potential mediator of stress-induced hippocampal malfunctions.

Animals

Establishment of a cBSA-mediated miRNA delivery system in Camellia sinensis and functional validation of the Cs-miR163/CsSK1 module in cold stress response.

Cold stress severely limits tea (Camellia sinensis) yield and quality. MicroRNAs (miRNAs) are key post-transcriptional regulators of plant cold responses; however, in vivo functional validation in tea plants is hindered by the lack of efficient genetic transformation and nucleic acid delivery systems. In this study, a cationized bovine serum albumin (cBSA)-mediated miRNA delivery system was established in tea plants. The cold-responsive miRNA Cs-miR163 and its target gene CsSK1 (a negative regulator of cold tolerance) were used as a model. Direct cleavage of CsSK1 mRNA by Cs-miR163 was confirmed by 5' RLM-RACE and GUS transient expression assays, and enhanced cold tolerance was demonstrated in Arabidopsis overexpression lines. The cBSA preparation protocol was optimized, yielding stable cBSA/miRNA complexes with high protective capacity across temperatures of 15-35 °C and pH 4.5-7.2. Delivery parameters were systematically evaluated; optimal conditions were determined as 2 mg/mL cBSA with 10 nM miRNA and solution uptake into 3-cm cuttings for 5 days, enhancing miRNA delivery efficiency by approximately 48-fold. Transmission electron microscopy provided direct ultrastructural evidence that cBSA/miRNA nanocomplexes are internalized into tea plant cells via adsorptive-mediated endocytosis involving electrostatic membrane adsorption, membrane invagination, and cytoplasmic release. Under optimized conditions, cBSA-mediated delivery of Cs-miR163 silenced CsSK1 expression by approximately 72%, reduced relative electrolyte leakage and ROS accumulation, and markedly enhanced cold tolerance. The regulatory role of the Cs-miR163/CsSK1 module was clarified, and the established system provides a promising strategy for functional genomics in woody plants that warrants further testing in additional species and tissues.

Camellia sinensis

Structural and functional characterization of peanut expansin proteins identifies AhEXPA3 as a stress-responsive regulator of seed germination.

Expansins are cell wall-associated proteins that play important roles in plant growth, development, and environmental responses, yet their structural features and functional significance in peanut remain insufficiently understood. Here, we performed a genome-wide identification and characterization of 70 expansin proteins in cultivated peanut. Phylogenetic analysis classified these genes into four subfamilies (EXPA, EXPB, EXLA, and EXLB), with conserved motif patterns and subgroup-specific exon-intron structures. Collinearity and evolutionary analyses revealed that segmental duplication mainly drove peanut expansin family expansion, with most duplicated gene pairs subsequently undergoing purifying selection. Promoter analysis identified abundant cis-regulatory elements associated with light responses, hormone signaling, and stress responses. Expression profiling indicated that many AhEXP genes were differentially expressed during seed germination and in response to abscisic acid (ABA), salt, and osmotic stresses. Among them, AhEXPA3 was identified as a stress-responsive expansin protein with marked transcriptional induction under abiotic stress conditions. Subcellular localization analysis suggested that AhEXPA3 exhibits an endoplasmic reticulum-associated localization pattern. Functional assays further demonstrated that heterologous expression of AhEXPA3 inhibited seed germination and early seedling establishment under stress conditions in both Arabidopsis thaliana and rice. These findings support a negative regulatory role of AhEXPA3 in stress-responsive seed germination and broaden current understanding of expansin protein function in legumes.

Germination

Advances in CRISPR multiplex gene editing to map and modify stress-responsive transcription factor networks for crop improvement.

The development of CRISPR multiplex genome-editing (MGE) tools is rapidly transforming plant functional genomics and accelerating crop improvements. By simultaneously targeting two or more DNA loci, it allows scientists to precisely edit multiple genes at the single-nucleotide level, within the target genome. Simultaneous manipulation of multiple targets has revolutionized the functional elucidation studies, particularly the dissection of complex genetic pathways. Due to its superior precision and feasibility, CRISPR-MGE is widely accepted and has largely replaced alternative editing tools such as TALENs and ZFNs. Several CRISPR-MGE strategies, including the use of individual expression cassettes, tRNA-processing enzymes, Csy4 or ribozymes, have been successfully deployed in plants. Recent advancements, such as Cpf1, transgene-free methods, or ultra-multiplexing approaches, have further refined the technology into a powerful, efficient, and robust toolkit. MGE enables complex genome editing, including multiple-gene knockouts, base alterations, transcriptional regulation, metabolic engineering, or their combinations. Consequently, it is ideal for elucidating the function of transcription factors that are key molecular players in regulating diverse plant responses, especially in stress pathways. Several stress-responsive TFs have been functionally characterized via CRISPR-MGE, and more advanced tools are being employed. This review evaluates multiplexing tools, their diverse applications, and the current progress toward developing advanced MGE tools. Ultimately, we provide evidence to encourage the use of advanced MGE tools for functional characterization studies of stress-responsive TFs, thereby highlighting their potential to accelerate crop improvement.

Gene Editing

Bimodal retrograde signaling disrupts a suppressor network and activates a key transcriptional activator to direct stress responses.

Plastid-to-nucleus communication, crucial for regulating stress-responsive gene expression, has long intrigued researchers. This study reveals how the plastidial metabolite 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) orchestrates transcriptional reprogramming by modulating the rapid stress response element (RSRE), a conserved regulatory hub in the plant general stress response network. Yeast one-hybrid assays identified HAT1, a class II HD-Zip protein, as a negative regulator of RSRE. Genetic analyses, including HAT1 overexpression and knockdowns, confirmed its role in suppressing RSRE activity. Interaction assays uncovered a suppression network involving HAT1, the co-repressor TOPLESS (TPL), and the nuclear importin IMPα-9. Furthermore, HAT1 interacts with calmodulin-binding transcription activator 3 (CAMTA3), a calcium/calmodulin-binding transcription factor known to activate RSRE. AlphaFold modeling provided insights into the architecture of the HAT1-RSRE complex and HAT-CAMTA3 interaction, supported by conserved domains across plant species. Under stress condition, MEcPP accumulation promotes the 26S proteasomal degradation of TPL and IMPα-9 while reduces auxin-dependent HAT1 expression. Additionally, MEcPP enhances Ca2+ influx, activating CAMTA3 and enabling it to bind RSRE, thereby initiating the transcription of stress response genes. This dual mechanism-dismantling suppressors (HAT1, TPL, and IMPα-9) and activating CAMTA3-underscores MEcPP's central role in plastid-to-nucleus signaling. These findings emphasize MEcPP's pivotal function in dynamically regulating gene expression to maintain cellular homeostasis under environmental stress.

Arabidopsis Proteins

Genome-wide characterization of heat shock protein genes reveals thermal stress-responsive candidates in Litopenaeus vannamei.

Heat shock proteins (HSPs) are conserved molecular chaperones involved in protein folding, refolding, aggregation prevention, and degradation of damaged proteins. However, the genomic organization and thermal responsiveness of HSP genes in the Pacific white shrimp (Litopenaeus vannamei) remain incompletely understood. Here, we performed a genome-wide analysis of the HSP gene family and examined its phylogenetic relationships, structural features, duplication patterns, sequence variation, interaction networks, and transcriptional responses to acute heat stress. A total of 34 HSP genes were identified and classified into the HSP90, HSP70, HSP40/DNAJ, HSP60, and small HSP families. Phylogenetic, motif, gene structure, synteny, and subcellular localization analyses revealed evolutionary conservation and structural diversification among family members. Three duplicated gene pairs were identified, comprising two segmental duplications and one tandem duplication. All pairs exhibited Ka/Ks ratios below 1, consistent with purifying selection of varying strength. Sequence analysis identified 295 nonsynonymous single-nucleotide polymorphisms, of which 12 were consistently predicted to be deleterious by multiple algorithms. Protein-protein interaction analysis indicated enrichment of protein-folding and cellular stress-response functions. RT-qPCR analysis showed significant induction of HSPA4, HSP90AA1, TRAP1, BiP, and DNAJA1 after 6, 12, and 24 h of exposure to 34 °C, whereas DNAJC3 was significantly induced only at 12 h. All six genes reached their highest transcript abundance at 12 h. These findings may provide a genomic framework for HSP genes in L. vannamei and identify candidate genes and variants associated with thermal stress responses.

Animals

Conserved HSFA1-dependent chromatin dynamics drive heat stress responses in plants.

Eukaryotic organisms remodel chromatin landscapes to regulate gene expression in response to environmental stress. In plants, heat stress (HS) induces widespread chromatin changes, yet the role of heat shock transcription factors (HSFs) in chromatin remodeling and their evolutionary conservation remains unclear. Using Marchantia polymorpha Mphsf mutants and Arabidopsis thaliana Athsfa1s mutants, we identify HSFA1 as a key regulator of HS-induced cis-regulatory element (CRE) accessibility, a mechanism conserved across land plants, mice, and humans. Gene regulatory network modeling reveals parallel transcription factor subnetworks, with MpWRKY10 and MpABI5B acting as indirect and negative HS regulators. We further showed that ABA modulates gene expression in an HSFA1-dependent manner without inducing chromatin remodeling. Finally, we develop a machine learning framework integrating chromatin accessibility and CRE information to predict gene expression across species, revealing stress-responsive regulatory logic at the transcriptional level. These findings provide insights into how TFs coordinate chromatin architecture to drive stress adaptation.

Heat-Shock Response

Stress response and its relationship to cystic (pseudofollicular) change in the definitive cortex of the adrenal gland in stillborn infants.

The adrenal glands of 41 fresh stillbirths were studied and a 'stress response' pattern could be seen in 28. In these glands the stress response was characterised by compact cell change, lipid depletion, excess pyroninophilia, and dilatation of the very prominent granular endoplasmic reticulum. Scattered areas of cytolysis of cells, especially of the definitive cortex, gave rise to the commonly seen cystic (pseudofollicular) change and it was obvious that cells undergoing lysis were severely 'stressed'. In 2 infants there was a 'clear cell reversal' pattern. Histological and ultrastructural changes of the stress response were not identified in 11. Infants of low birthweight score were somewhat more commonly represented in the group that did not show a stress response. Cytolytic changes accompanying a stress response were commoner in immature infants. It is argued that cystic (pseudofollicular) change in the adrenal cortex of the newborn signifies a previous stress reaction.

Adrenal Cortex

PSEUDO-RESPONSE REGULATOR 3b and transcription factor ABF3 modulate abscisic acid-dependent drought stress response in soybean.

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.

Glycine max

From activation to desensitization: How ABA balances plant growth and abiotic stress response?

Abscisic acid (ABA) signaling is a central regulator of plant adaptation to abiotic stress, dynamically coordinating stress responses with growth and development. Rapid activation of ABA signaling promotes plant survival during the early stages of stress, whereas prolonged stress requires timely attenuation of the pathway to restore growth and prevent excessive stress responses. Recent studies have uncovered diverse mechanisms underlying ABA desensitization, including regulation of SnRK2 kinases, phytohormone crosstalk, nutrient signaling, protein trafficking, post-translational modifications, and feedback regulatory networks. Together, these interconnected mechanisms enable plants to fine-tune ABA signaling in response to developmental and environmental cues. In this review, we summarize recent advances in understanding the molecular mechanisms that attenuate ABA signaling and restore the balance between growth and stress adaptation during prolonged stress. We also highlight outstanding questions and discuss strategies for engineering ABA signaling dynamics to improve crop resilience, productivity, and adaptation to increasingly variable environments.

Abscisic Acid

A field study of the stress response syndrome. Young women after hysterectomy.

The symptom pattern previously delineated as the stress response syndrome in a mental health setting was hypothesized to be useful in conceptualizing reactions to a traumatic event in a nonpsychiatric patient population. The experience of loss resulting from nonelective hysterectomy for benign disease in women of childbearing age was selected as a relevant field study model. Twenty-eight women were studied one year after hysterectomy, using extensive psychological interviewing by women clinicians and experiential rating scales. Twelve subjects had a mild stress response syndrome, and five subjects had a serious level of intrusive and avoidant symptoms. Increasing severity of response was associated with persisting child-wish, deterioration in sexual functioning, and change in self-concept. Women who did well postoperatively generally had no future wish for children and were actively committed to achievement outside of the home.

Adaptation, Psychological

Oxidative stress induces E. coli aryl polyene expression, sensitizing the bacterial stress response and modulating the redox environment of innate immune cells.

UNLABELLED: Aryl polyenes (APEs) are specialized polyunsaturated outer membrane lipids that protect their producers from oxidative stress and contribute to biofilm formation. APEs are produced by an abundant biosynthetic gene cluster (BGC) family conserved across Gram-negative bacterial clades. The APE biosynthesis pathway involves 11 different enzymes and culminates in the attachment of APEs to an anchor molecule in the Gram-negative outer membrane. Unlike most other small molecule BGCs, the APE BGC does not contain a dedicated regulatory gene that controls the production of its metabolically costly compounds. Building from our prior observations of APEs' role in acute oxidative stress protection, we use a uropathogenic Escherichia coli (UPEC) strain to show that APE expression conveys a potential competitive advantage characterized by increased early-stage growth, sensitization of the bacterial oxidative stress response, and dampening of the redox stress of innate immune cells after in vitro infection. Our data indicate that APEs could act as a UPEC fitness factor, and in future work, we aim to study their contribution to overall bacterial pathogenicity and survival, as well as how APEs could facilitate the transition from an oxygen-poor environment, such as the gut, to the oxygen-rich environment of the urinary tract. IMPORTANCE: Bacterial pathogens use various mechanisms to achieve a competitive advantage under harsh conditions, such as during interactions with their host. We studied the function of aryl polyenes (APEs), specialized polyunsaturated fatty acids in the outer membrane, in the context of a uropathogenic E. coli strain. APE expression is induced by an oxidative environment and contributes to early-stage growth and sensitization of the oxidative stress response. Furthermore, APE-expressing E. coli dampen the intracellular oxidative milieu of target host phagocytes. These findings suggest a role for APEs as a fitness factor and create opportunities to study their in vivo function and explore them as a potential drug target.

Oxidative Stress

Genome-Wide Association Analysis of Hippocampal Neuroplasticity as an Indicator of Stress Responsiveness in Laying Hens (Gallus gallus domesticus).

Environmental stressors in commercial poultry systems can negatively affect bird welfare, although individuals vary considerably in their responses. Neuroplasticity within the hippocampus, measured through the density of doublecortin-positive (DCX+) neurons, provides a potential biomarker of stress experience in laying hens. However, the genetic basis underlying variation in this biomarker remains poorly understood. A total of 42 H&N and Hy-Line Brown hens housed in a multitier free range and enriched cage system, respectively, were genotyped using Genotyping by Sequencing, yielding over 200 000 SNP markers after initial filtering. Hippocampal tissue sections were immunostained for DCX to quantify the density of highly plastic neurons. A genome-wide association analysis identified 19 genomic regions across eight chromosomes within the top 1% of windows explaining the greatest proportion of genetic variance in the neuroplasticity phenotype. Within ±100 kb of these regions, 39 annotated genes were identified, several of which are involved in cellular regulation and genetic information processing pathways. Notably, PIK3R6, VPS37D, STX1A, BAZ1B, HGH1, MAF1, MAPK15, and PIT54 emerged as positional candidate genes potentially contributing to variation in stress responsiveness. These findings provide preliminary insight into the genetic architecture of hippocampal neuroplasticity in laying hens and highlight candidate genes that may contribute to individual differences in stress response, with potential implications for breeding strategies aimed at improving poultry welfare.

Animals

Assessing the genetic potential of a milk mid-infrared prediction of heat stress response in dairy cows using a temperature-humidity index-independent approach.

Selection for heat tolerance remains challenging due to the difficulty of accessing reliable phenotypes at large scale. An alternative could be established using mid-infrared spectra, which are collected routinely through milk recording, and have already shown their value as proxies for a variety of phenotypes that are costly or difficult to measure. Recently, a first prediction of heat stress response in dairy cows based solely on milk mid-infrared spectra was developed. This prediction was obtained using models calibrated on surface body temperature and milk composition variations. Its potential as a detection tool was explored, but no genetic analyses has been performed. On this basis, the objectives of this study were to estimate the heritability of the predicted heat stress response, assess its genetic correlations with traits from the Walloon official genetic evaluation, and identify genomic regions associated with heat tolerance through a GWAS, all without using temperature-humidity index (THI) information. The estimated heritability (0.10) was low but sufficient to enable genetic selection and consistent with expectations for a heat stress-related trait. Also as expected, an antagonistic relationship between heat tolerance and milk production was observed, but its extent was notably reduced compared with traditional approaches. In addition, genetic correlations with other traits were neutral (fat yield) or favorable (protein yield, SCS, fertility, longevity). Concerning the GWAS, genomic regions and candidate genes previously associated with the response to heat stress were highlighted, as well as others related to energy balance maintenance. Overall, these results support the relevance of the prediction for the heat stress response as a new phenotype for heat tolerance selection that does not require any THI information. They also reinforce the importance of energy balance for dairy cows to cope with heat stress.

Journal Article

BCLAF1 restrains stress responses in hematopoietic stem cells to support expansion and repopulation.

Hematopoietic stem cells (HSCs) rapidly expand during fetal development and after stress. Here, we identify B-cell lymphoma-2-associated factor 1 (BCLAF1) as a regulator of HSC repopulation activity, with roles in the expansion of fetal HSCs and hematopoietic reconstitution after stem cell transplantation. Using mice with hematopoietic-specific and inducible deletion of Bclaf1, we find that BCLAF1 promotes fetal HSC development but is dispensable for the maintenance of adult HSCs at steady state. Loss of BCLAF1 in either fetal or adult HSCs significantly impairs their self-renewal and multilineage reconstitution activity after stem cell transplantation. Single-cell RNA sequencing of fetal hematopoietic progenitors reveals that loss of BCLAF1 reduces long-term HSCs and restrains the expression of stress response genes. BCLAF1 associates with chromatin throughout the genome of fetal and adult hematopoietic cells, likely through indirect mechanisms, to regulate transcriptional programs. These results establish a novel function for the transcriptional regulator BCLAF1 in limiting stress responses in HSCs, thereby preserving HSC development during embryogenesis and repopulation function after stem cell transplant.

Hematopoietic Stem Cells