Types Of Progenitors Research Articles

Human-specific ARHGAP11B ensures human-like basal progenitor levels in hominid cerebral organoids.

The human-specific gene ARHGAP11B has been implicated in human neocortex expansion. However, the extent of ARHGAP11B's contribution to this expansion during hominid evolution is unknown. Here we address this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. ARHGAP11B expression in chimpanzee cerebral organoids doubles basal progenitor levels, the class of cortical progenitors with a key role in neocortex expansion. Conversely, interference with ARHGAP11B's function in human cerebral organoids decreases basal progenitors down to the chimpanzee level. Moreover, ARHGAP11A or ARHGAP11B rescue experiments in ARHGAP11A plus ARHGAP11B double-knockout human forebrain organoids indicate that lack of ARHGAP11B, but not of ARHGAP11A, decreases the abundance of basal radial glia - the basal progenitor type thought to be of particular relevance for neocortex expansion. Taken together, our findings demonstrate that ARHGAP11B is necessary and sufficient to ensure the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human-specific gene was a major contributor to neocortex expansion during human evolution.

Human‐specific ARHGAP11B ensures human‐like basal progenitor levels in hominid cerebral organoids

The human‐specific gene ARHGAP11B has been implicated in human neocortex expansion. However, the extent of ARHGAP11B's contribution to this expansion during hominid evolution is unknown. Here we address this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. ARHGAP11B expression in chimpanzee cerebral organoids doubles basal progenitor levels, the class of cortical progenitors with a key role in neocortex expansion. Conversely, interference with ARHGAP11B's function in human cerebral organoids decreases basal progenitors down to the chimpanzee level. Moreover, ARHGAP11A or ARHGAP11B rescue experiments in ARHGAP11A plus ARHGAP11B double‐knockout human forebrain organoids indicate that lack of ARHGAP11B, but not of ARHGAP11A, decreases the abundance of basal radial glia—the basal progenitor type thought to be of particular relevance for neocortex expansion. Taken together, our findings demonstrate that ARHGAP11B is necessary and sufficient to ensure the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human‐specific gene was a major contributor to neocortex expansion during human evolution.

LB1016 Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer

In the mammalian skin epidermis, it has long been unclear how molecularly heterogenous stem/progenitor cell populations fit into the complete trajectory of epidermal differentiation. Here, we combine in vivo imaging with single-cell RNA sequencing to define the early stages of epidermal stem cell differentiation at the molecular and behavioral level. We show that differentiation, from commitment to exit from the stem cell layer, is a multi-day process wherein cells transit through a gradual continuum of transcriptional changes. By tracking epidermal regions over many days, we find that differentiation-committed cells remain capable of dividing to produce daughter cells fated to further differentiate, demonstrating that differentiation is uncoupled from cell cycle exit. These cell divisions occur as a response to local density changes, and are not required as part of an obligate transit amplifying program but instead help to buffer the differentiating cell pool upon disruption of the epidermal barrier. Thus, instead of distinct contributions from multiple progenitor types, a single continuous differentiation process shaped by feedback from the local environment fuels lifelong turnover of the epidermis.

Analysis of Single Blood Entities Using an Ultramicroelectrode through Single-Entity Electrochemistry

The research was conducted with the aim of analyzing individual human blood cells in the presence of redox species based on single-entity electrochemistry. Various blood cells (e.g., red blood cell, white blood cell, and platelets) perform a role directly related to survival, such as oxygen transport, hemostasis, and immune response, as they move through the whole body’s blood vessels. However, with the current lab-on-a-chip typed biosensor technology, the factors that can be measured using a small amount of blood are limited to uric acid, cholesterol, glucose, or hemoglobin in the blood. In clinical laboratories, common methods for measuring individual blood counts are automated hematology analyzers based on the automated Coulter cell counting method or flow cytometry, which produce a huge amount of blood count results, but are limited. For this reason, it is proposed a method for detecting individual blood cells that can be applied to a biosensor simply and quickly.References Ran, An. et al. (2021) ‘Emerging point-of-care technologies for anemia detection’, Lab on a Chip, 21(10), pp. 1843-1865.J-H, Lin. et al. (2020) ‘A Multifunctional Microfluidic Device for Blood Typing and Primary Screening of Blood Diseases’ ACS Sensors, 5(10), pp. 3082-3090.J, Lee. et al. (2020) ‘Determination of Serotonin Concentration in Single Human Platelets through Single-Entity Electrochemistry’, ACS Sensors, 5(7), pp. 1943-1948.T.L.T, Ho. et al. (2018) ‘Determining mean corpuscular volume and red blood cell count using electrochemical collision events’, Biosensors and Bioelectronics. 110, pp. 155-159.A-C, Villani. et al. (2017) ‘Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors’, Science. 356, No.6335.

Models of Millimeter and Radio Emission from Interacting Supernovae

This work utilizes established models of synchrotron-powered light curves for core-collapse supernovae in dense circumstellar environments, namely, type IIn and Ibn, to demonstrate the potential for detecting millimeter emission from these events. The progenitor types of these supernovae are still an open question, but using the synchrotron light curves as probes for the circumstellar environments could shed light on the mass-loss histories of the progenitors and discern between different theories. Observations in millimeter bands are particularly fruitful, as they probe regions at smaller radii and higher ambient densities, where centimeter emission tends to be self-absorbed. In our application of these light curves, we explore a diversity of progenitor types and mass-loss profiles to understand their effects on the light-curve shapes. Additionally, we fit model parameters to the 8 GHz light curve of type IIn supernova 2006jd and then create millimeter light curves using these parameters to show the possibility of detecting an early millimeter peak from such an event. We predict that next generation millimeter surveys will possess the capability to detect nearby and extreme events. However, there is a pressing need for millimeter follow-up of optically discovered interacting supernovae to more completely sample the true population.

Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy

Various types of progenitors initiate individual organ formation and their crosstalk orchestrates morphogenesis for the entire embryo. Here we show that progenitor exosomal communication across embryonic organs occurs in normal development and is altered in embryos of diabetic pregnancy. Endoderm fibroblast growth factor 2 (FGF2) stimulates mesoderm Flk-1+ vascular progenitors to produce exosomes containing the anti-stress protein Survivin. These exosomes act on neural stem cells of the neuroepithelium to facilitate neurulation by inhibiting cellular stress and apoptosis. Maternal diabetes causes Flk-1+ progenitor dysfunction by suppressing FGF2 through DNA hypermethylation. Restoring endoderm FGF2 prevents diabetes-induced survivin reduction in Flk-1+ progenitor exosomes. Transgenic Survivin expression in Flk-1+ progenitors or in utero delivery of survivin-enriched exosomes restores cellular homeostasis and prevents diabetes-induced neural tube defects (NTDs), whereas inhibiting exosome production induces NTDs. Thus, functional inter-organ communication via Flk-1 exosomes is vital for neurulation and its disruption leads to embryonic anomalies.

The proliferative and multipotent epidermal progenitor cells for human skin reconstruction in vitro and in vivo.

ObjectivesThe skin exhibits tremendous regenerative potential, as different types of progenitor and stem cells regulate skin homeostasis and damage. However, in vitro primary keratinocytes present with several drawbacks, such as high donor variability, short lifespan, and limited donor tissue availability. Therefore, more stable primary keratinocytes are needed to generate multiple uniform in vitro and in vivo skin models.ResultsWe identified epidermal progenitor cells from primary keratinocytes using Integrin beta 1 (ITGB1) an epidermal stem cell marker markedly decreased after senescence in vitro. Epidermal progenitor cells exhibited unlimited proliferation and the potential for multipotent differentiation capacity. Moreover, they could completely differentiate to form an organotypic skin model including conversed mesenchymal cells in the dermis and could mimic the morphologic and biochemical processes of human epidermis. We also discovered that proliferation and the multipotent differentiation capacity of these cells relied on ITGB1 expression. Eventually, we examined the in vitro and in vivo wound healing capacity of these epidermal progenitor cells.ConclusionsOverall, the findings suggest that these stable and reproducible cells can differentiate into multiple lineages, including human skin models. They are a potentially powerful tool for studying skin regeneration, skin diseases, and are an alternative for in vivo experiments.

A deep learning approach to halo merger tree construction

ABSTRACT A key ingredient for semi-analytic models of galaxy formation is the mass assembly history of haloes, encoded in a tree structure. The most commonly used method to construct halo merger histories is based on the outcomes of high-resolution, computationally intensive N-body simulations. We show that machine learning (ML) techniques, in particular Generative Adversarial Networks (GANs), are a promising new tool to tackle this problem with a modest computational cost and retaining the best features of merger trees from simulations. We train our GAN model with a limited sample of merger trees from the Evolution and Assembly of GaLaxies and their Environments (EAGLE) simulation suite, constructed using two halo finders–tree builder algorithms: SUBFIND – D-TREES and ROCKSTAR – ConsistentTrees. Our GAN model successfully learns to generate well-constructed merger tree structures with high temporal resolution, and to reproduce the statistical features of the sample of merger trees used for training, when considering up to three variables in the training process. These inputs, whose representations are also learned by our GAN model, are mass of the halo progenitors and the final descendant, progenitor type (main halo or satellite), and distance of a progenitor to that in the main branch. The inclusion of the latter two inputs greatly improves the final learned representation of the halo mass growth history, especially for SUBFIND-like ML trees. When comparing equally sized samples of ML merger trees with those of the EAGLE simulation, we find better agreement for SUBFIND-like ML trees. Finally, our GAN-based framework can be utilized to construct merger histories of low- and intermediate-mass haloes, the most abundant in cosmological simulations.

Developmental dynamics of two bipotent thymic epithelial progenitor types

T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age1–10. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice11–18; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved1,12,16,17,19–27. Here we combine scRNA-seq and a new CRISPR–Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity.

On LGRB progenitors: An approach from thermally-produced neutrinos

Gamma-ray bursts (GRB) are the most intense electromagnetic (EM) sources in the Universe. Long GRB (LGRB) correspond to those events with a typical prompt emission of more than a few seconds. It is generally assumed that they are originated after an implosion of a very massive star within a central compact object engine that can be either a black hole (BH) or a rapidly-spinning highly-magnetized neutron star (NS). Nevertheless, one of the most challenging aspects of defining a unique model is that the progenitor remains initially hidden for direct EM observation. In this work, we investigate the evolution of thermally-produced neutrino properties in both GRB progenitors to provide an alternative solution. We consider the characteristics of both progenitors and the fireball scenario to calculate the oscillation probabilities within a three-flavor admixture regime. Then we obtain the expected neutrino ratio and we also estimate the number of events from these sources that could be detected in the future Hyper-Kamiokande (Hyper-K) detector, considering a sample of previously observed GRB with remarkably signs of being magnetar-produced. Our findings indicate that examining the predicted neutrino rates result in an additional mechanism to determine the type of progenitor associated with these events. This is especially useful when, for instance, we cannot directly observe an electromagnetic counterpart, such as so-called “failed” GRB with hidden jets, or when light curve analysis is inconclusive.

Progenitor-Based Cell Biological Aspects of Neocortex Development and Evolution.

During development, the decision of stem and progenitor cells to switch from proliferation to differentiation is of critical importance for the overall size of an organ. Too early a switch will deplete the stem/progenitor cell pool, and too late a switch will not generate the required differentiated cell types. With a focus on the developing neocortex, a six-layered structure constituting the major part of the cerebral cortex in mammals, we discuss here the cell biological features that are crucial to ensure the appropriate proliferation vs. differentiation decision in the neural progenitor cells. In the last two decades, the neural progenitor cells giving rise to the diverse types of neurons that function in the neocortex have been intensely investigated for their role in cortical expansion and gyrification. In this review, we will first describe these different progenitor types and their diversity. We will then review the various cell biological features associated with the cell fate decisions of these progenitor cells, with emphasis on the role of the radial processes emanating from these progenitor cells. We will also discuss the species-specific differences in these cell biological features that have allowed for the evolutionary expansion of the neocortex in humans. Finally, we will discuss the emerging role of cell cycle parameters in neocortical expansion.

Evolution Toward the Observational Features of a Stripped Envelope Type IIb Supernova in a Binary System

Type IIb supernovae (SNe IIb) that have a thin layer of hydrogen left in their outer envelope have been believed to belong to core collapse supernovae. Mass transfer via Roche lobe overflow can significantly change the nucleosynthesis and surface chemical elements of the progenitors of SNe IIb. We aim to explore what conditions a close binary can meet with the observational features of SNe IIb. We find that an observed low mass SN IIb cannot be produced by a low mass isolated star with M < 20 M ⊙ due to the existence of a thick hydrogen envelope regardless of rotation. Binaries dominate as progenitors in the mass interval (i.e., M < 20 M ⊙) considered in this paper. The 16 M ⊙ primary with a 14 M ⊙ companion in a binary system with ∼10 days < P orb < 720 days can reproduce observational features of SNe IIb (i.e., T eff, , M He, M H, etc.). With the decrease of the hydrogen-rich envelope mass, the radius of the progenitor shrinks. The associated types of SN IIb progenitors from RSGs and YSGs to BSGs are closely related to the amount of hydrogen left in the envelopes. Rotation can bring the production of the CNO reaction to the stellar surface at an early phase, which would explain the nitrogen-rich circumstellar material of SN 1993J and can also explain the large He/H ratio of supernova ejecta. Rotation can increase the corresponding region of the orbital period which can produce an SN IIb.

Stem Cells, Hematopoiesis and Lineage Tracing: Transplantation-Centric Views and Beyond.

An appropriate production of mature blood cells, or hematopoiesis, is essential for organismal health and homeostasis. In this developmental cascade, hematopoietic stem cells (HSCs) differentiate into intermediate progenitor types, that subsequently give rise to the many distinct blood cell lineages. Here, we describe tools and methods that permit for temporal and native clonal-level HSC lineage tracing in the mouse, and that can now be combined with emerging single-cell molecular analyses. We integrate new insights derived from such experimental paradigms with past knowledge, which has predominantly been derived from transplantation-based approaches. Finally, we outline current knowledge and novel strategies derived from studies aimed to trace human HSC-derived hematopoiesis.

Recombinant Limb Assay as in Vivo Organoid Model.

Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled in vitro by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an in vivo organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties in vivo from these cells for the first time.

Multiple cell populations generate macrophage progenitors in the early yolk sac.

Yolk sac (YS) CSF1 receptor positive (CSF1R+) cells are thought to be the progenitors for tissue-resident macrophages present in various tissues. The YS progenitors for tissue-resident macrophages are referred to as erythroid-myeloid progenitors (EMPs). However, diverse types of hematopoietic progenitors are present in the early YS, thus it is not precisely known which type of hematopoietic cell gives rise to the CSF1R+ lineage. In this study, an analysis was conducted to determine when CSF1R+ progenitors appeared in the early YS. It showed that CSF1R+ cells appeared in the YS as early as embryonic day 9 (E9) and that the earliest hematopoietic progenitors that differentiate into CSF1R+ cells were found in E8. Since these progenitors possessed the capability to generate primitive erythroid cells, it was likely that primitive erythroid lineages shared progenitors with the CSF1R+ lineage. Mutual antagonism appears to work between PU.1 and GATA1 when CSF1R+ cells appear in the early YS. One day later (E9), multiple progenitors, including myeloid-restricted progenitors and multipotent progenitors, in the YS could immediately generate CSF1R+ cells. These results suggest that EMPs are not an exclusive source for the CSF1R+ lineage; rather, multiple hematopoietic cell populations give rise to CSF1R+ lineage in the early YS.

Resurrection of Nonthermal Emissions from Type Ib/c Supernova Remnants

Abstract Supernova remnants (SNRs) are important objects in investigating the links among supernova (SN) explosion mechanism(s), progenitor stars, and cosmic-ray acceleration. Nonthermal emission from SNRs is an effective and promising tool for probing their surrounding circumstellar media (CSM) and, in turn, the stellar evolution and mass-loss mechanism(s) of massive stars. In this work, we calculate the time evolution of broadband nonthermal emissions from Type Ib/c SNRs, whose CSM structures are derived from the mass-loss history of their progenitors. Our results predict that Type Ib/c SNRs make a transition of brightness in radio and γ-ray bands from an undetectable dark for a certain period to a rebrightening phase. This transition originates from their inhomogeneous CSM structures in which the SNRs are embedded within a low-density wind cavity surrounded by a high-density wind shell and the ambient interstellar medium (ISM). The “resurrection” in nonthermal luminosity happens at an age of ∼1000 yr old for a Wolf-Rayet star progenitor evolved within a typical ISM density. Combining with the results of Type II SNR evolution recently reported by Yasuda et al., this result sheds light on a comprehensive understanding of nonthermal emissions from SNRs with different SN progenitor types and ages, which is made possible for the first time by the incorporation of realistic mass-loss histories of the progenitors.

Evolution of Somite Compartmentalization: A View From Xenopus.

Somites are transitory metameric structures at the basis of the axial organization of vertebrate musculoskeletal system. During evolution, somites appear in the chordate phylum and compartmentalize mainly into the dermomyotome, the myotome, and the sclerotome in vertebrates. In this review, we summarized the existing literature about somite compartmentalization in Xenopus and compared it with other anamniote and amniote vertebrates. We also present and discuss a model that describes the evolutionary history of somite compartmentalization from ancestral chordates to amniote vertebrates. We propose that the ancestral organization of chordate somite, subdivided into a lateral compartment of multipotent somitic cells (MSCs) and a medial primitive myotome, evolves through two major transitions. From ancestral chordates to vertebrates, the cell potency of MSCs may have evolved and gave rise to all new vertebrate compartments, i.e., the dermomyome, its hypaxial region, and the sclerotome. From anamniote to amniote vertebrates, the lateral MSC territory may expand to the whole somite at the expense of primitive myotome and may probably facilitate sclerotome formation. We propose that successive modifications of the cell potency of some type of embryonic progenitors could be one of major processes of the vertebrate evolution.

Tracing the skeletal progenitor transition during postnatal bone formation

Multiple distinct types of skeletal progenitors have been shown to contribute to endochondral bone development and maintenance. However, the division of labor and hierarchical relationship between different progenitor populations remain undetermined. Here we developed dual-recombinase fate-mapping systems to capture the skeletal progenitor transition during postnatal bone formation. We showed that postnatal osteoblasts arose primarily from chondrocytes before adolescence and from Lepr+ bone marrow stromal cells (BMSCs) after adolescence. This transition occurred in the diaphysis during adolescence and progressively spread to the metaphysis. The osteoblast-forming Lepr+ BMSCs derived primarily from fetal Col2+ cells. Conditional deletion of Runx2 from perinatal chondrocytes and adult Lepr+ BMSCs impaired bone lengthening and thickening, respectively. Forced running increased osteoblast formation by perinatal chondrocytes but not by adult Lepr+ BMSCs. Thus, the short-term developmental skeletal progenitors generated the long-term adult skeletal progenitors. They sequentially control the growth and maintenance of endochondral bones.

From Progenitors to Progeny: Shaping Striatal Circuit Development and Function.

Understanding how neurons of the striatum are formed and integrate into complex synaptic circuits is essential to provide insight into striatal function in health and disease. In this review, we summarize our current understanding of the development of striatal neurons and associated circuits with a focus on their embryonic origin. Specifically, we address the role of distinct types of embryonic progenitors, found in the proliferative zones of the ganglionic eminences in the ventral telencephalon, in the generation of diverse striatal interneurons and projection neurons. Indeed, recent evidence would suggest that embryonic progenitor origin dictates key characteristics of postnatal cells, including their neurochemical content, their location within striatum, and their long-range synaptic inputs. We also integrate recent observations regarding embryonic progenitors in cortical and other regions and discuss how this might inform future research on the ganglionic eminences. Last, we examine how embryonic progenitor dysfunction can alter striatal formation, as exemplified in Huntington's disease and autism spectrum disorder, and how increased understanding of embryonic progenitors can have significant implications for future research directions and the development of improved therapeutic options.SIGNIFICANCE STATEMENT This review highlights recently defined novel roles for embryonic progenitor cells in shaping the functional properties of both projection neurons and interneurons of the striatum. It outlines the developmental mechanisms that guide neuronal development from progenitors in the embryonic ganglionic eminences to progeny in the striatum. Where questions remain open, we integrate observations from cortex and other regions to present possible avenues for future research. Last, we provide a progenitor-centric perspective onto both Huntington's disease and autism spectrum disorder. We suggest that future investigations and manipulations of embryonic progenitor cells in both research and clinical settings will likely require careful consideration of their great intrinsic diversity and neurogenic potential.

Identification of Pre-Gmps and Pre-Meps: Two Novel Types of Committed Progenitor Cells in Bone Marrow

Elucidating the stepwise differentiation processes that leads from multipotent hematopoietic stem cells to mature effector cells is critical for understanding both normal and neoplastic hematopoiesis. Early studies suggested that common myeloid progenitors (CMPs) are oligo-lineage hematopoietic progenitors that produce all lineages of myeloid cells, including granulocytes, monocytes, erythrocytes and megakaryocytes. CMPs do so by first giving rise to megakaryocyte-erythroid progenitors (MEPs) and granulocyte-monocyte progenitors (GMPs), two types of bi-lineage progenitors. However, this concept was challenged by several recent studies where single cell techniques demonstrated that CMPs, GMPs and MEPs are highly heterogenic. The existence of lineage-restricted subsets within the CMP population leads to questions about whether erythroid and megakaryocytic lineage commitment is actually initiated at the multipotent progenitor or CMP stage. During the past 15 years, several lineage-restricted subsets of progenitors have been separated out from CMP population, including monocyte-dendritic progenitors, megakaryocyte progenitors, and erythroid progenitors based on expression of CD115/Flt3, CD41/CD150, and CD105/CD150, respectively. However, the remaining CMP population is still highly heterogenic. Thus, further separation of functional subsets within the CMP compartment is required.By screening cell surface markers that can further separate CMPs, we have identified CD27 as a reliable marker to separate all megakaryocyte/erythrocyte-committed progenitors from granulocyte/monocyte-committed progenitors. In addition, we found that CD62L is only expressed on granulocyte/monocyte-committed progenitors. CD27 and CD62L co-staining can separate CMP into CD27 +CD62L +, CD27 +CD62L - and CD27 -CD62L - subsets. Biology and morphology study showed that CD27 +CD62L - cells are closely associated with GMPs, whereas CD27 -CD62L - cells are closely associated with MEPs. In vitro culture and in vivo transplantation functional studies demonstrated that 1) CD27 +CD62L + cells are pre-GMPs that give rise to FcGRII/III + GMPs and only produce granulocytes and monocytes; 2) CD27 -CD62L - cells are pre-MEPs that give rise to MEPs and primarily produce erythrocytes and megakaryocytes with minimal contribution to granulocytes and monocytes; 3) CD27 +CD62L - subset enriches cells with genuine CMP potential capable of producing GMPs, MEPs, and subsequent progeny. Taken together, we have identified two novel populations of committed progenitors that serve as intermediates between CMP-GMP and CMP-MEP commitment pathways. Identification of pre-GMPs and pre-MEPs fills in the gap between CMPs-GMPs and CMPs-MEPs, supporting the hierarchal relationship of myeloid lineage differentiation. DisclosuresNo relevant conflicts of interest to declare.