Savage AM , Alberio R , Johnson AD .

BB/ T013575/1 Biotechnology and Biological Sciences Research Council

             regeneration

	Fig. 1. Specification of PGCs in non-rodent mammals and primates display similarities during gastrulation despite differential PGC markers during earlier development. (A) Porcine embryos form an amnion after implantation, while (B) primate embryos (illustrated by cynomolgus monkey) form an amnion before implantation. SOX17/BLIMP1+ cells are observed in the porcine posterior epiblast prior to gastrulation, while similar cells are observed in the amnion of primates. However, during gastrulation in both species, increased numbers of PGCs are observed in the posterior epiblast. At E13 pig and E17 cynomolgus monkey, yellow cells indicate T+; SOX17+; TFAP2C+ PGCs induced in GLCM, purple cells indicate migratory SOX17+; TFAP2C+; BLIMP1+ PGCs. Image created in Biorender.
	Fig. 2. Potential stem cell differentiation hierarchy in bPGC species. In species which specify PGCs via GLCM, different stem cell types (including HSCs) may also be specified simultaneously and therefore directly share ancestry with PGCs. Image created in Biorender.
	Fig. 3. Predicted basal vertebrate migratory route for PGCs and HSCs. In Carnegie stage 10 (∼21 days in human embryos) bPGC embryos, pre-migratory bipotential progenitors are associated with the hindgut; Carnegie stage 12 (∼27 days in human embryos) bPGC embryos display migratory cells expressing both PGC and HSC markers. These cells colonise both the genital ridges and ventral wall of the DA, suggesting they respond stochastically to migratory cues from each tissue. Image created in Biorender.
	Fig. 4. Engraftment into different niches can confer a new identify on stem cells. Studies have shown that stem cells are capable of producing cell types relevant to the somatic tissue onto which they are engrafted, suggesting a plasticity of stem cell nature. Image created in Biorender.

Alberio, Conserved features of non-primate bilaminar disc embryos and the germline. 2021, Pubmed

Alberio, Conserved features of non-primate bilaminar disc embryos and the germline. 2021, Pubmed
Aramaki, A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. 2013, Pubmed
Bachvarova, Gene expression in the axolotl germ line: Axdazl, Axvh, Axoct-4, and Axkit. 2004, Pubmed
BECKER, Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. 1963, Pubmed
Bertrand, Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. 2005, Pubmed
Bertrand, Haematopoietic stem cells derive directly from aortic endothelium during development. 2010, Pubmed
Braat, Characterization of zebrafish primordial germ cells: morphology and early distribution of vasa RNA. 1999, Pubmed
Brown, Two different network topologies yield bistability in models of mesoderm and anterior mesendoderm specification in amphibians. 2014, Pubmed , Xenbase
Burns, Hematopoietic stem cell fate is established by the Notch-Runx pathway. 2005, Pubmed
Buske, Overexpression of HOXA10 perturbs human lymphomyelopoiesis in vitro and in vivo. 2001, Pubmed
Bussmann, Early endocardial morphogenesis requires Scl/Tal1. 2007, Pubmed
Butko, Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. 2015, Pubmed
Chatfield, Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos. 2014, Pubmed , Xenbase
Chen, Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. 2009, Pubmed
Chen, Germline competency of human embryonic stem cells depends on eomesodermin. 2017, Pubmed
Chen, Human Primordial Germ Cells Are Specified from Lineage-Primed Progenitors. 2019, Pubmed
Chuva de Sousa Lopes, Primordial germ cell specification: the importance of being 'blimped'. 2008, Pubmed
Ciau-Uitz, Distinct origins of adult and embryonic blood in Xenopus. 2000, Pubmed , Xenbase
Crosse, Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development. 2020, Pubmed
de Bruijn, Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. 2000, Pubmed
de Bruijn, Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta. 2002, Pubmed
de Pater, Gata2 is required for HSC generation and survival. 2013, Pubmed
Detrich, Intraembryonic hematopoietic cell migration during vertebrate development. 1995, Pubmed
Deveau, Epigenetic therapy restores normal hematopoiesis in a zebrafish model of NUP98-HOXA9-induced myeloid disease. 2015, Pubmed
Easterbrook, Analysis of the Spatiotemporal Development of Hematopoietic Stem and Progenitor Cells in the Early Human Embryo. 2019, Pubmed
Ema, Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. 2000, Pubmed
Fidanza, Single-cell analyses and machine learning define hematopoietic progenitor and HSC-like cells derived from human PSCs. 2020, Pubmed
Ganuza, Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs. 2018, Pubmed
Gering, The SCL gene specifies haemangioblast development from early mesoderm. 1998, Pubmed , Xenbase
Gerritsen, RUNX1 mutations enhance self-renewal and block granulocytic differentiation in human in vitro models and primary AMLs. 2019, Pubmed
Growney, Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. 2005, Pubmed
Hartung, Zebrafish vasa is required for germ-cell differentiation and maintenance. 2014, Pubmed
Hiyama, Telomere and telomerase in stem cells. 2007, Pubmed
Houston, A critical role for Xdazl, a germ plasm-localized RNA, in the differentiation of primordial germ cells in Xenopus. 2000, Pubmed , Xenbase
Huber, Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. 2004, Pubmed
Irie, SOX17 is a critical specifier of human primordial germ cell fate. 2015, Pubmed
Jeong, BMP4 and perivascular cells promote hematopoietic differentiation of human pluripotent stem cells in a differentiation stage-specific manner. 2020, Pubmed
Johnson, Evolution of predetermined germ cells in vertebrate embryos: implications for macroevolution. 2003, Pubmed
Johnson, Primordial germ cells: the first cell lineage or the last cells standing? 2015, Pubmed
Johnson, Expression of axolotl DAZL RNA, a marker of germ plasm: widespread maternal RNA and onset of expression in germ cells approaching the gonad. 2001, Pubmed , Xenbase
Johnson, Regulative germ cell specification in axolotl embryos: a primitive trait conserved in the mammalian lineage. 2003, Pubmed
Jokubaitis, Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues. 2008, Pubmed
Kalev-Zylinska, Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis. 2002, Pubmed
Kanatsu-Shinohara, Pluripotency of a single spermatogonial stem cell in mice. 2008, Pubmed
Kanatsu-Shinohara, Generation of pluripotent stem cells from neonatal mouse testis. 2004, Pubmed
Khattak, Germline transgenic methods for tracking cells and testing gene function during regeneration in the axolotl. 2013, Pubmed , Xenbase
Kissa, Blood stem cells emerge from aortic endothelium by a novel type of cell transition. 2010, Pubmed
Kissa, Live imaging of emerging hematopoietic stem cells and early thymus colonization. 2008, Pubmed
Knaut, Zebrafish vasa RNA but not its protein is a component of the germ plasm and segregates asymmetrically before germline specification. 2000, Pubmed
Knudsen, ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation. 2015, Pubmed
Kobayashi, On the origin of the human germline. 2018, Pubmed
Kobayashi, Principles of early human development and germ cell program from conserved model systems. 2017, Pubmed
Kodama, Neurogenic potential of progenitors derived from human circulating CD14+ monocytes. 2006, Pubmed
Kojima, Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells. 2017, Pubmed
Kucia, A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. 2006, Pubmed
Kucia, Identification of very small embryonic like (VSEL) stem cells in bone marrow. 2008, Pubmed
Kurimoto, Specification of the germ cell lineage in mice: a process orchestrated by the PR-domain proteins, Blimp1 and Prdm14. 2008, Pubmed
Lai, Xenopus Nanos1 is required to prevent endoderm gene expression and apoptosis in primordial germ cells. 2012, Pubmed , Xenbase
Lawrence, Mice bearing a targeted interruption of the homeobox gene HOXA9 have defects in myeloid, erythroid, and lymphoid hematopoiesis. 1997, Pubmed
Lawrence, Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells. 2005, Pubmed
Lawson, Bmp4 is required for the generation of primordial germ cells in the mouse embryo. 1999, Pubmed
Leopardo, Early embryonic development and spatiotemporal localization of mammalian primordial germ cell-associated proteins in the basal rodent Lagostomus maximus. 2017, Pubmed
Li, Dual fluorescent reporter pig for Cre recombination: transgene placement at the ROSA26 locus. 2014, Pubmed
Lis, Conversion of adult endothelium to immunocompetent haematopoietic stem cells. 2017, Pubmed
Lopez, Mapping hematopoiesis in a fully regenerative vertebrate: the axolotl. 2014, Pubmed
Marass, Genome-wide strategies reveal target genes of Npas4l associated with vascular development in zebrafish. 2019, Pubmed
McGarvey, A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. 2017, Pubmed
McLaren, How is the mouse germ-cell lineage established? 2005, Pubmed
Medvinsky, Definitive hematopoiesis is autonomously initiated by the AGM region. 1996, Pubmed
Méndez-Ferrer, Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. 2010, Pubmed
Moghaddam, Differentiation potential of human CD133 positive hematopoietic stem cells into motor neuron- like cells, in vitro. 2017, Pubmed
Molyneaux, Primordial germ cell migration. 2004, Pubmed
Moore, Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo. 2018, Pubmed
Murayama, Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. 2006, Pubmed
Nagai, Early hematopoietic and vascular development in the chick. 2018, Pubmed
North, Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. 1999, Pubmed
North, Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. 2002, Pubmed
Oberlin, Blood-forming potential of vascular endothelium in the human embryo. 2002, Pubmed
Ohinata, Blimp1 is a critical determinant of the germ cell lineage in mice. 2005, Pubmed
Okuda, AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. 1996, Pubmed
Olsen, A vasa-like gene in zebrafish identifies putative primordial germ cells. 1997, Pubmed
Padrón-Barthe, Clonal analysis identifies hemogenic endothelium as the source of the blood-endothelial common lineage in the mouse embryo. 2014, Pubmed
Palis, Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. 1999, Pubmed
Plein, Erythro-myeloid progenitors contribute endothelial cells to blood vessels. 2018, Pubmed
Qian, Distinct functions for different scl isoforms in zebrafish primitive and definitive hematopoiesis. 2007, Pubmed
Reischauer, Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification. 2016, Pubmed
Reynaud, SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment. 2005, Pubmed
Rich, Primordial germ cells are capable of producing cells of the hematopoietic system in vitro. 1995, Pubmed
Richardson, Mechanisms guiding primordial germ cell migration: strategies from different organisms. 2010, Pubmed
Rybtsov, Tracing the origin of the HSC hierarchy reveals an SCF-dependent, IL-3-independent CD43(-) embryonic precursor. 2014, Pubmed
Saleque, The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. 2002, Pubmed
Sasaki, Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells. 2015, Pubmed
Sasaki, The Germ Cell Fate of Cynomolgus Monkeys Is Specified in the Nascent Amnion. 2016, Pubmed
Scaldaferri, Hematopoietic activity in putative mouse primordial germ cell populations. 2015, Pubmed
Schultz, When stem cells grow old: phenotypes and mechanisms of stem cell aging. 2016, Pubmed
Selvaratnam, Male Rat Germ Cells Display Age-Dependent and Cell-Specific Susceptibility in Response to Oxidative Stress Challenges. 2015, Pubmed
Shah, MYB bi-allelic targeting abrogates primitive clonogenic progenitors while the emergence of primitive blood cells is not affected. 2021, Pubmed
Shaikh, Mouse Bone Marrow VSELs Exhibit Differentiation into Three Embryonic Germ Lineages and Germ & Hematopoietic Cells in Culture. 2017, Pubmed
Silver, Initiation of murine embryonic erythropoiesis: a spatial analysis. 1997, Pubmed
SIMINOVITCH, THE DISTRIBUTION OF COLONY-FORMING CELLS AMONG SPLEEN COLONIES. 1963, Pubmed
Sinka, Angiotensin-converting enzyme (CD143) specifies emerging lympho-hematopoietic progenitors in the human embryo. 2012, Pubmed
Soza-Ried, Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. 2010, Pubmed
Stainier, Cloche, an early acting zebrafish gene, is required by both the endothelial and hematopoietic lineages. 1995, Pubmed
Stefanska, Primitive erythrocytes are generated from hemogenic endothelial cells. 2017, Pubmed
Sugimura, Haematopoietic stem and progenitor cells from human pluripotent stem cells. 2017, Pubmed
Surani, Mechanism of mouse germ cell specification: a genetic program regulating epigenetic reprogramming. 2004, Pubmed
Sutasurja, The induction of the primordial germ cells in the urodeles. 1974, Pubmed
Tanabe, Transdifferentiation of human adult peripheral blood T cells into neurons. 2018, Pubmed
Tang, A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. 2015, Pubmed
Taoudi, Functional identification of the hematopoietic stem cell niche in the ventral domain of the embryonic dorsal aorta. 2007, Pubmed
Tavian, Aorta-associated CD34+ hematopoietic cells in the early human embryo. 1996, Pubmed
Tavian, Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo. 1999, Pubmed
Taylor, Placental growth factor (PlGF) enhances breast cancer cell motility by mobilising ERK1/2 phosphorylation and cytoskeletal rearrangement. 2010, Pubmed
Taylor, Hematopoietic stem cell activity in the aorta-gonad-mesonephros region enhances after mid-day 11 of mouse development. 2010, Pubmed
Thambyrajah, A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis. 2016, Pubmed
Thompson, The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis. 1998, Pubmed
TILL, A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. 1961, Pubmed
Tipping, High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle. 2009, Pubmed
Tsai, Ca2+ signaling in cytoskeletal reorganization, cell migration, and cancer metastasis. 2015, Pubmed
Venkatarama, Repression of zygotic gene expression in the Xenopus germline. 2010, Pubmed , Xenbase
Wang, Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. 1996, Pubmed
Weidinger, dead end, a novel vertebrate germ plasm component, is required for zebrafish primordial germ cell migration and survival. 2003, Pubmed , Xenbase
Wilkinson, Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta. 2009, Pubmed
Wu, A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells. 1967, Pubmed
Yamaguchi, Nanog expression in mouse germ cell development. 2005, Pubmed
Yang, Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo. 2015, Pubmed
Yoon, Zebrafish vasa homologue RNA is localized to the cleavage planes of 2- and 4-cell-stage embryos and is expressed in the primordial germ cells. 1997, Pubmed
Zhang, Efficient sequencing of Anuran mtDNAs and a mitogenomic exploration of the phylogeny and evolution of frogs. 2013, Pubmed
Zipori, The nature of stem cells: state rather than entity. 2004, Pubmed