Single-cell transcriptomic analysis identifies an immune-prone population in erythroid precursors during human ontogenesis.

Nonimmune cells can have immunomodulatory roles that contribute to healthy development. However, the molecular and cellular mechanisms underlying the immunomodulatory functions of erythroid cells during human ontogenesis remain elusive. Here, integrated, single-cell transcriptomic studies of erythroid cells from the human yolk sac, fetal liver, preterm umbilical cord blood (UCB), term UCB and adult bone marrow (BM) identified classical and immune subsets of erythroid precursors with divergent differentiation trajectories. Immune-erythroid cells were present from the yolk sac to the adult BM throughout human ontogenesis but failed to be generated in vitro from human embryonic stem cells. Compared with classical-erythroid precursors, these immune-erythroid cells possessed dual erythroid and immune regulatory networks, showed immunomodulatory functions and interacted more frequently with various innate and adaptive immune cells. Our findings provide important insights into the nature of immune-erythroid cells and their roles during development and diseases.

Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage.

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression, but also injures the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on transplanted human HSCs have not been studied. Here, we report that RIBE impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further analyses revealed that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell-cycle arrest, and p53-dependent apoptosis, mainly because of oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies in vitro and in vivo. Taken together, these findings suggest that RIBE impair human HSCs and HPCs by oxidative DNA damage. This study provides definitive evidence for RIBE on transplanted human HSCs and further justifies the necessity of conducting clinical trials to evaluate different antioxidants to improve the efficacy of HSC transplantation for the patients with hematological or nonhematological disorders.

Effective Faraday rotator based on the TbYO3 crystal with a high Verdet constant and a high thermal conductivity.

Facing the demand of high-power laser development, a high-quality magneto-optical crystal with a high Verdet constant and a high thermal conductivity is needed. Herein, an effective Faraday rotation based on a TbYO3 single crystal with a strong magneto-optical effect, grown by the laser floating zone method, is demonstrated for the first time, to the best of our knowledge. The TbYO3 crystal has the Verdet constant which is 2.16 times (106 rad·m-1 T-1) higher than that of the TGG crystal (49 rad·m-1 T-1) at 880 nm. Additionally, the TbYO3 crystal also has a thermal conductivity of 11.8 W·m-1·K-1 and a laser-induced damage threshold of 1.59 GW·cm-2. These advantages can allow the TbYO3 crystal to be an attractive magneto-optical material.

Bone marrow endothelial cell-derived interleukin-4 contributes to thrombocytopenia in acute myeloid leukemia.

Normal hematopoiesis can be disrupted by the leukemic bone marrow microenvironment, which leads to cytopenia-associated symptoms including anemia, hemorrhage and infection. Thrombocytopenia is a major and sometimes fatal complication in patients with acute leukemia. However, the mechanisms underlying defective thrombopoiesis in leukemia have not been fully elucidated. In the steady state, platelets are continuously produced by megakaryocytes. Using an MLL-AF9-induced acute myeloid leukemia mouse model, we demonstrated a preserved number and proportion of megakaryocyte-primed hematopoietic stem cell subsets, but weakened megakaryocytic differentiation via both canonical and non-canonical routes. This primarily accounted for the dramatic reduction of megakaryocytic progenitors observed in acute myeloid leukemia bone marrow and a severe disruption of the maturation of megakaryocytes. Additionally, we discovered overproduction of interleukin-4 from bone marrow endothelial cells in acute myeloid leukemia and observed inhibitory effects of interleukin-4 throughout the process of megakaryopoiesis in vivo Furthermore, we observed that inhibition of interleukin-4 in combination with induction chemotherapy not only promoted recovery of platelet counts, but also prolonged the duration of remission in our acute myeloid leukemia mouse model. Our study elucidates a new link between interleukin-4 signaling and defective megakaryopoiesis in acute myeloid leukemia bone marrow, thereby offering a potential therapeutic target in acute myeloid leukemia.

A Retrospective Propensity Score Matched Study of the Preoperative C-Reactive Protein to Albumin Ratio and Prognosis in Patients with Resectable Non-Metastatic Breast Cancer.

BACKGROUND A retrospective study aimed to investigate the association between the CRP to albumin ratio and prognosis in patients with resectable non-metastatic breast cancer in terms of disease-free survival (DFS) and overall survival (OS) using propensity score matching. MATERIAL AND METHODS Patients with newly diagnosed resectable non-metastatic breast cancer (n=200) who underwent modified radical mastectomy between January 2008 to June 2013 included a group with an increased CRP to albumin ratio ≥0.029 (n=80) and a group with reduced CRP to albumin ratio <0.029 (n=120). Propensity score matching was used to estimate the prognostic role of the CRP to albumin ratio, and a 1: 1 matching using four covariates was performed to overcome selection bias. The prognostic significance of the CRP to albumin ratio was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and a Cox proportional hazards model were conducted to identify the impact on DFS and OS. RESULTS An increased CRP to albumin ratio was associated with increased age, post-menopausal status, and a high risk of recurrence or death in patients with breast cancer. An increased preoperative CRP to albumin ratio was significantly associated with reduced disease-free survival (DFS) and overall survival (OS) (all P<0.05). Multivariate analysis showed that an increased CRP to albumin ratio was an independent risk factor for long-term outcome and predicted reduced DFS (HR, 2.225; P=0.024) and OS (HR, 9.189; P=0.003). CONCLUSIONS Preoperative evaluation of the CRP to albumin ratio was an independent prognostic indicator in patients with resectable breast cancer.

Intron 1 GATA site enhances ALAS2 expression indispensably during erythroid differentiation.

The first intronic mutations in the intron 1 GATA site (int-1-GATA) of 5-aminolevulinate synthase 2 (ALAS2) have been identified in X-linked sideroblastic anemia (XLSA) pedigrees, strongly suggesting it could be causal mutations of XLSA. However, the function of this int-1-GATA site during in vivo development remains largely unknown. Here, we generated mice lacking a 13 bp fragment, including this int-1-GATA site (T AGATAA: AGCCCC) and found that hemizygous deletion led to an embryonic lethal phenotype due to severe anemia resulting from a lack of ALAS2 expression, indicating that this non-coding sequence is indispensable for ALAS2 expression in vivo Further analyses revealed that this int-1-GATA site anchored the GATA site in intron 8 (int-8-GATA) and the proximal promoter, forming a long-range loop to enhance ALAS2 expression by an enhancer complex including GATA1, TAL1, LMO2, LDB1 and Pol II at least, in erythroid cells. However, compared with the int-8-GATA site, the int-1-GATA site is more essential for regulating ALAS2 expression through CRISPR/Cas9-mediated site-specific deletion. Therefore, the int-1-GATA site could serve as a valuable site for diagnosing XLSA in cases with unknown mutations.

Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation.

Cytopenias resulting from the impaired generation of normal blood cells from hematopoietic precursors are important contributors to morbidity and mortality in patients with leukemia. However, the process by which normal hematopoietic cells are overtaken by emerging leukemia cells and how different subsets of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are distinctly influenced during leukemic cell infiltration is poorly understood. To investigate these important questions, we used a robust nonirradiated mouse model of human MLL-AF9 leukemia to examine the suppression of HSCs and HPCs during leukemia cell expansion in vivo. Among all the hematopoietic subsets, long-term repopulating HSCs were the least reduced, whereas megakaryocytic-erythroid progenitors were the most significantly suppressed. Notably, nearly all of the HSCs were forced into a noncycling state in leukemic marrow at late stages, but their reconstitution potential appeared to be intact upon transplantation into nonleukemic hosts. Gene expression profiling and further functional validation revealed that Egr3 was a strong limiting factor for the proliferative potential of HSCs. Therefore, this study provides not only a molecular basis for the more tightened quiescence of HSCs in leukemia, but also a novel approach for defining functional regulators of HSCs in disease.

ATF4 plays a pivotal role in the development of functional hematopoietic stem cells in mouse fetal liver.

The fetal liver (FL) serves as a predominant site for expansion of functional hematopoietic stem cells (HSCs) during mouse embryogenesis. However, the mechanisms for HSC development in FL remain poorly understood. In this study, we demonstrate that deletion of activating transcription factor 4 (ATF4) significantly impaired hematopoietic development and reduced HSC self-renewal in FL. In contrast, generation of the first HSC population in the aorta-gonad-mesonephros region was not affected. The migration activity of ATF4(-/-) HSCs was moderately reduced. Interestingly, the HSC-supporting ability of both endothelial and stromal cells in FL was significantly compromised in the absence of ATF4. Gene profiling using RNA-seq revealed downregulated expression of a panel of cytokines in ATF4(-/-) stromal cells, including angiopoietin-like protein 3 (Angptl3) and vascular endothelial growth factor A (VEGFA). Addition of Angptl3, but not VEGFA, partially rescued the repopulating defect of ATF4(-/-) HSCs in the culture. Furthermore, chromatin immunoprecipitation assay in conjunction with silencing RNA-mediated silencing and complementary DNA overexpression showed transcriptional control of Angptl3 by ATF4. To summarize, ATF4 plays a pivotal role in functional expansion and repopulating efficiency of HSCs in developing FL, and it acts through upregulating transcription of cytokines such as Angptl3 in the microenvironment.

High repetition rates optically active langasite electro-optically Q-switched laser at 1.34 µm.

An electro-optically Q-switched pulsed laser at 1.34 µm with a repetition rate of 100 kHz applying optically active langasite (La3Ga5SiO14) crystal has been reported. With Nd:YVO4 as laser crystal, the electro-optically Q-switched pulsed lasers were obtained with the maximum repetition rate of 100 kHz, maximum average output power of 2.42 W, and a minimum pulse width of 2.4 ns. Based on the theory of rate equations, the optimal pulse energy of the electro-optical Q-switching could be calculated. The experimental results have been found to be matched well with the theoretical calculations. To the best of our knowledge, this work presents the highest repetition rate and shortest pulse width which are achieved by an electric-optic LGS Q-switching at the wavelength of 1.34 µm, and it enriches the material categories for generating the high repetition rate pulsed laser.

Predictive Value of Circulating Tumor Cells for Evaluating Short- and Long-Term Efficacy of Chemotherapy for Breast Cancer.

BACKGROUND The present study investigated the role of circulating tumor cells (CTCs) counts in predicting the short- and long-term efficacy of chemotherapy for breast cancer (BC). MATERIAL AND METHODS Peripheral venous blood was extracted from 187 BC patients. CTCs were measured by flow cytometry. Spearman's correlation analysis was performed to examine the correlation between the efficacy of chemotherapy and CTC counts. A receiver operating characteristic (ROC) curve was plotted to estimate the predictive value of CTC counts. The Kaplan-Meier method was employed to calculate disease-free survival (DFS) and overall survival (OS). Cox regression analysis was used to determine risk factors for prognosis of BC. RESULTS Complete response (CR) + partial response (PR) was achieved by 65.8% of BC patients. After chemotherapy, CTC counts were decreased in both the CR + PR and SD + PD groups. Spearman's correlation analysis indicated that CTC counts before chemotherapy were positively correlated with clinical response to chemotherapy (r=0.45, P<0.05). For predicting clinical response to chemotherapy, CTC counts yielded an area under the curve (AUC) of 0.958, with sensitivity reaching 96.9% and specificity reaching 85.4%. The Kaplan-Meier method and Cox regression analysis indicated that tumor node metastasis (TNM) staging, lymph node metastasis (LNM), ki-67, endocrine therapy, and CTC counts were risk factors for prognosis of BC. CONCLUSIONS These findings indicate that BC patients with CTCs ³8 exhibited poor response to chemotherapy and poor OS. CTC counts can serve as an indicator in predicting short- and long-term efficacy of chemotherapy for BC.

Hematopoietic stem cell regeneration enhanced by ectopic expression of ROS-detoxifying enzymes in transplant mice.

High levels of reactive oxygen species (ROS) can exhaust hematopoietic stem cells (HSCs). Thus, maintaining a low state of redox in HSCs by modulating ROS-detoxifying enzymes may augment the regeneration potential of HSCs. Our results show that basal expression of manganese superoxide dismutase (MnSOD) and catalase were at low levels in long-term and short-term repopulating HSCs, and administration of a MnSOD plasmid and lipofectin complex (MnSOD-PL) conferred radiation protection on irradiated recipient mice. To assess the intrinsic role of elevated MnSOD or catalase in HSCs and hematopoietic progenitor cells, the MnSOD or catalase gene was overexpressed in mouse hematopoietic cells via retroviral transduction. The impact of MnSOD and catalase on hematopoietic progenitor cells was mild, as measured by colony-forming units (CFUs). However, overexpressed catalase had a significant beneficial effect on long-term engraftment of transplanted HSCs, and this effect was further enhanced after an insult of low-dose γ-irradiation in the transplant mice. In contrast, overexpressed MnSOD exhibited an insignificant effect on long-term engraftment of transplanted HSCs, but had a significant beneficial effect after an insult of sublethal irradiation. Taken together, these results demonstrate that HSC function can be enhanced by ectopic expression of ROS-detoxifying enzymes, especially after radiation exposure in vivo.

Toward Professionalism of Biobanking in China: A Survey on Working Status, Career Development, Challenges, and Prospects of Biobankers.

Biobanking has become an increasingly important activity to provide resources for medical research support. In China, establishing and maintaining a biobank have been the latest trend in a research hospital. However, biobanking is still an emerging young field in terms of professionalization and professionalism. The development of professionalization in biobanking faces many challenges involving the development of skills, identities, norms, and values associated with becoming part of a professional group. Biobanking professionals (i.e., biobankers) are the most important factor and driving force toward professionalization in biobanking. To better understand biobankers' performance, needs, concerns, and career development, we conducted two comprehensive surveys among biobankers in China in 2019 and 2021, respectively. The questionnaires covered four major areas: (1) basic information and the status of biobankers; (2) job performance evaluation, salary, recognitions, rewards, and so on; (3) occupational training and career development; and (4) challenges and prospects and so on. The surveys revealed that most biobankers in China have positive working attitudes and a high desire for their future career development, but due to the uncertain evaluation mechanisms and promotion routes, etc., the participants were more optimistic about biobanking development compared to the biobanker's career development (77.0% and 57.4% respectively in 2021, p < 0.05). The biobankers expected more training opportunities and salary packages. Because biobankers are an integral factor and driving force to ensure the successful biobanking operation and advancement, the survey data analysis revealed interesting findings and references for the development of professionalism in biobanking. This survey will provide first-hand information to governments, biobank management teams, and the general public to further support, promote, or optimize (1) biobanking operation and sustainability, (2) biobankers' career development, (3) biobank management and quality control, and (4) strategic plans and approaches to establish a higher quality professional team of biobankers.

High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcgamma receptors on monocytes in patients with primary immune thrombocytopenia.

The human Fcγ receptor (FcγR) system is composed of 2 opposing families, the activating FcγRs (FcγRI, FcγRIIa, and FcγRIII) and the inhibitory FcγR (FcγRIIb). The disturbed balance of the activating and inhibitory FcγRs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of FcγRs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The FcγRI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of FcγRIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of FcγRIIb mRNA and protein coincided with a remarkable decrease in the expression of FcγRIIa, FcγRI, and monocyte phagocytic capacity. There was no significant difference in FcγRIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce FcγRIIa and FcγRIIb expression in monocytes from ITP patients, with FcγRIIb at higher amplitudes. These findings suggested that the disturbed FcγR balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte FcγR balance toward the inhibitory FcγRIIb in patients with ITP.

Self-Raman 1176 nm Laser Generation from Nd:YVO4 Crystal by Resonator Cavity Coating.

Crystal coating is an important process in laser crystal applications. According to the crystal characteristics of neodymium-doped yttrium vanadate (Nd:YVO4), its intrinsic parameters, and optical film design theory, Ta2O5 and SiO2 were selected separately as high and low refractive index materials. The optical properties and surface roughness of the films were characterized by OptiLayer and Zygo interferometers, and the effects of ion source bias on refractive index and surface roughness were investigated so that the optimal ion source parameters were determined. Optical monitoring and quartz crystal control were combined to accurately control the thickness of each film layer and to reduce the monitoring error of film thickness. The prepared crystal device was successfully applied to the 1176 nm laser output system.

Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100Ahigh immunoregulatory neutrophil progenitors, immunophenotyped as Lin-CD34+CD66b+CD177+, than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Myelodysplastic syndromes are multiclonal diseases derived from hematopoietic stem and progenitor cells.

Myelodysplastic syndromes (MDS) are generally considered as a group of clonal diseases derived from hematopoietic stem cells, but a number of studies have suggested that they are derived from myeloid progenitor cells. We aimed to identify the cell of origin in MDS by single-cell analyses. Targeted single-cell RNA sequencing, covering six frequently mutated genes (U2AF1, SF3B1, TET2, ASXL1, TP53, and DNMT3A) in MDS, was developed and performed on individual cells isolated from the CD34+ and six lineage populations in the bone marrow of healthy donors (HDs) and patients with MDS. The detected mutations were used as clonal markers to define clones. By dissecting the distribution of clones in six lineages, the clonal origin was determined. We identified three mutations both in HDs and patients with MDS, termed clonal hematopoiesis (CH) mutations. We also identified fifteen mutations only detected in patients with MDS, termed MDS mutations. Clonal analysis showed that CH clones marked by CH mutations and MDS clones marked by MDS mutations were derived from hematopoietic stem cells as well as various hematopoietic progenitor cells. Most patients with MDS showed the chimeric state with CH clones and MDS clones. Clone size analysis suggested that CH mutations may not contribute to clonal expansion of MDS. In conclusion, MDS comprise multiple clones derived from hematopoietic stem and progenitor cells.

Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9+ and HES1+ cells from Lin-CD34+CD45RA- HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9+Lin-CD34+CD45RA- HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9+Lin-CD34+CD45RA- HSPCs was 3-fold higher than that of the CD9- counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9- HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9+Lin-CD34+CD45RA- HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.

Temporal molecular program of human hematopoietic stem and progenitor cells after birth.

Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases.